Biomedical subjects
Publications and source records attributed to M L Griem.
The author contends that neutron radiation therapy coupled with radiation therapy or other forms of particle radiation therapy may play a role in the management of malignant gliomas. Improved survival, particularly for the patients with the diagnosis of glioblastoma, is discussed.
No significant tumor increase was found in the initial analysis of patients irradiated for peptic ulcer and followed through 1962. A preliminary study was undertaken 22 years later to estimate the risk of cancer due to gastric irradiation for peptic ulcer disease. A population of 2,049 irradiated patients and 763 medically managed patients has been identified. A relative risk of 3.7 was found for stomach cancer and an initial risk estimate of 5.5 X 10(-6) excess stomach cancers per person rad was calculated. A more complete follow-up is in progress to further elucidate this observation and decrease the ascertainment bias; however, preliminary data are in agreement with the Japanese atomic bomb reports.
The effects of single doses of X radiation ranging from 200 to 2000 rad were studied by direct morphometry in vivo of the mature, stable microvasculature in rabbit ear chambers. Reproducible observations in vivo of the mature microvasculature were obtained by photomicrography of identical 0.033-mm2 sites in each ear chamber prior to and 1 and 5 days following single doses of X radiation. Measurements were made directly on color photomicrographs at a total magnification of 2000X. The microvessels were divided into two groups according to size: vessels greater than 10 microns in diameter (arterioles and venules), and vessels less than or equal to 10 microns in diameter (capillaries). Vascular length and outer and inner surface areas were measured directly on the projected photomicrographs, and vascular volumes and diameters were calculated from these measured parameters. Measurements of capillary length per unit surface area disclosed a decrease in capillary density with increasing dose, resulting in a calculated intercapillary distance in excess of 300 microns, conceivably associated with a decrease in oxygen delivery by the microvasculature. With this method, radiosensitivity of the capillaries was found to be significantly greater than that of larger vessels. Computerized histogram analysis of vascular length, surface area, and volume as a function of increasing diameter (1-micron bins) confirmed the significant difference in reduction of these measured parameters between the capillaries and the larger vessels. The total microvascular volume profile dominated by the volume of larger vessels did not change much 5 days after irradiation, although capillary volume was markedly reduced. Furthermore, the basic profile of the microvasculature showed a shift to larger diameters following irradiation, thus confirming the calculated dilatation of surviving vessels. Qualitative morphologic observations revealed considerable extravasation from the microvessels and formation of micropetechiae at the site of disrupted capillaries with subsequent inflammatory changes.
The cellular outgrowths from three layers of rabbit and monkey aorta were used as primary cultures. Irradiation of the tissue fragments at the time of explanation resulted in a reduction in outgrowth of 50% with a dose of 200 rad, and in a reduction of over 90% with doses of 300 rad and above. When comparable cultures were irradiated after 2 months in vitro as a mature actively metabolizing but slowly proliferating cell population, radioresistance was increased. Subcultures of medial smooth muscle cells irradiated during their logarithmic growth phase showed a linear dose response in the cell number parameter up to 150 rad. A dose of 250 rad resulted in complete flattening of the growth curve, with a reduction in labeling index, after a 3-hr terminal [3H]TdR pulse. On the other hand, the labeling index indicated some recovery 3 days after irradiation in cultures receiving less than 250 rad. Under the same experimental conditions, cells derived from the intima of the same aorta showed no recovery when increase in cell numbers over time, or the number of labeled cells per area, were used as parameters. Cells derived from adventitia showed a relative increase in the number of labeled cells per area 4 and 7 days after irradiation following an initial decrease on Day 1.
The authors present a case of radiation-induced pacemaker failure. After 2,000 rad (20 Gy) of photon irradiation for metastatic bronchogenic carcinoma, the pulse generator circuitry failed, producing a "runaway" rhythm. This suggests that present pacemaker circuitry may be more susceptible to irradiation than previously believed, and that even modest radiation doses can induce life-threatening arrhythmias.
A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situations requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which "maximum likelihood estimates" of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data. These TOC curves suggest, however, that treatment doses greater than 1800 ret may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors.
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In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease.
Nine patients with medulloblastoma were referred to the Radiation Oncology Section at the University of Chicago from 1966 to 1976. In all patients, the tumor was situated in the posterior cranial fossa, projecting from the cerebellum into the fourth ventricle. After partial tumor resection and histological diagnosis, radiation treatment was instituted: a localized dose of 1000 rad to the posterior fossa through lateral opposing ports and a total dose of 4000-5000 rad through the "hockey-stick" port to the entire CNS. With this treatment, 9 patients yielded actuarial 3- and 5-year survival rates of 88% and 73%, respectively. Five of the patients possessed no history of neurologic or spinal growth deficits after treatment. Two patients had a slight retardation of spinal growth. The remaining patients had presented symptoms of a tumor mass in the posterior fossa for a period of over 8 months prior to treatment. They were found at craniectomy to have diffuse intracranial tumor involvement, and their survival times deteriorated rapidly. The "hockey-stick" port provided a uniform distribution of radiation exposure to the entire brain and spine. It was simple to use and posed little inconvenience to patients in the pediatric age group.
The patients with the typical clinical course and pathology of Mycosis Fungoides (MF) were found also to have Hodgkin's Disease (HD), nodular sclerosing type. In two cases, HD was diagnosed 2 years after the diagnosis of MF; in the third case, both diseases were diagnosed simultaneously. Previous claims of MF transforming into second lymphomas are reviewed. The possible significance of our observed association of MF and HD is discussed.
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In a comprehensive mycosis fungoides program, 60 patients have been seen with a pathologic diagnosis of this disease. Forty-four patients with advanced disease were referred for radiation therapy. Three treatment techniques were identified in which 14 patients were treated with localized fields using electrons or whole-body electron-beam therapy with doses of less than 3000 rads, 21 patients were treated using the Stanford technique with tissue doses of between 3000 and 4000 rads, and nine patients were treated with six cycles of mechlorethamine, vincristine, prednisone, and procarbazine or cyclophosphamide, vincristine, prednisone, and procarbazine following the electron-beam therapy. The actuarial survival rate was 45% at 1 year for the 14 patients with localized electron-beam therapy, whereas the actuarial survival rates were 83% for patients treated with whole-body electron-beam therapy and 100% for patients treated with whole-body electron-beam therapy followed by four-drug chemotherapy. The recurrence-free interval for these three groups correlates with these observations. A central nervous system recurrence has been observed in the combined-therapy group.
Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, I(E), II, II(E). Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved-field radiotherapy. The survival rate and relapse-free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.
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