Changes in cytotoxicity and viability of immune lymphocytes after X-irradiation.
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Biomedical subjects
Publications and source records attributed to S H Levitt.
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Accurate dose prediction for megavoltage photon therapy of carcinoma of the esophagus requires information on tumor depth, lung thickness, and lung density. The authors found that CT localization of internal and external contours is accurate within +/- 1 mm. Lung density can be measured with an error of less than 0.02 g/cm3 in the range 0.25-1.00 g/cm3. Variance between predicted and measured dosage was less than 3% in all patients and in most RANDO phantom measurements. Accurate radiation therapy planning is possible with CT information from a commercial scanner.
The protection of the upper thoracic spine achieved by a tube-tilt technique was found to be comparable to that obtained from direct shielding during cross-fire therapy of the intrathoracic esophagus. An isocentric technique was utilized which included one anterior and two posterior-oblique fields. Significant underdosages to the esophagus at levels superior to the isocenter are caused by tube-tilt, whereas direct shielding resulted in a uniformity of esophageal doses to within 5%. The need for a tissue compensator for the anterior field must be assessed on an individual basis from off-axis treatment planning.
In electron beam therapy, alterations in dosimetry occur as a result of air space between the end-of-treatment cone and the skin surface. A large air gap may be introduced in order to obtain a field size larger than that available at the cone end. Needed dosimetry corrections related to these air space problems are discussed, along with a proposed method of measuring effective source-to-cone end distance. Data presented show the modifications of a dosimetric field which occur with an increase in the air space below the treatment cone.
The authors describe an independent minicomputer consisting of a CRT and a cassette unit which was designed to store patient data and interact with the main computer at a convenient time. This system permits the computer to handle data entry and treatment planning functions simultaneously. The layout of the overall system, the function of the program and a time analysis of the system are discussed.
The effect of 5-thio-D-glucose on chronically hypoxic cells in the multicell spheroids of Chinese hamster V79 cells was investigated. The radiation survival curves of spheroid cells indicated that most of the chronically hypoxic cells in the spheroids could be eliminated by incubating the spheroids with 5-20 mM of 5-thio-D-glucose or 17 hours. Histological studies also demonstrated that 5-thio-D-glucose preferentially kills the hypoxic cells located in the inner part of the spheroids.
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The effect of 5-thio-D-glucose on oxic and hypoxic V79-171 Chinese hamster cells was studied in vitro with single cells and multicell spheroids. At concentrations that were not toxic to oxic cells, this compound killed hypoxic cells with a D0 of 1 hr with a 5 mM concentration and more rapidly at 10 mM beginning 2 hr after incubation at 37 degrees. 5-Thio-D-glucose also sensitized hypoxic cells to radiation and protected oxic cells from radiation damage. Multicell spheroids irradiated after incubation with the compound demonstrated increased radiosensitivity, although the relative contribution of cytotoxicity and hypoxic cell sensitization could not be evaluated. Spheroid reoxygenation by decreased cell respiration was determined not to be a contributing factor, suggesting that the spheroid-sensitizing effect was due to drug effects on hypoxic cells. The dramatic increase in multicell spheroid radiosensitivity that resulted from treatment with 5-thio-D-glucose suggests that this compound may be used to increase the effectiveness of radiotherapy by eliminating hypoxic protection.
(1) Radiotherapy after definitive surgery for breast cancer has not been proved to have a deleterious effect on patient survival. (2) The beneficial effect of radiation therapy is to decrease significantly local recurrences (P less than .001), which are very difficult to control once they develop. (3) In the hands of experienced radiotherapists, the incidence of complications is quite low. (4) Adjuvant chemotherapy effects on the prevention of local recurrence are most encouraging but still experimental and should at this stage be used mainly in study situations. (5) Until more detailed information is obtained, radiation therapy remains the most effective, least toxic method for the control of local disease.
A statistical assessment of several "randomized" clinical trials was carried out and the following conclusions were noted. 1. There is no statistically significant evidence that radiation to the peripheral lymphatics and/or chest wall following radical mastectomy affects survival. 2. There is significant evidence that postoperative irradiation to the peripheral lymphatics and/or chest wall does decrease local recurrence rate. 3. There is reliable evidence that the treatment of local recurrence, once it develops, is successful in only 50% of the cases. 4. There is evidence that radiation plus simple mastectomy is as effective in the treatment of breast cancer as radical mastectomy alone. It is our considered opinion that radiation remains a useful adjuvant and complementary agent in the treatment of breast cancer, is not harmful vis a vis survival and should be used when and where indicated.
A re-examination of the statistical methods used to develop the claim that radiation postoperatively decreases survival was carried out. This study demonstrates that a) when correct figures are used, statistical significance is not demonstrated, i.e. there is not statistically significant evidence that irradiation of the peripheral lymphatics and/or chest wall following mastectomy has a deleterious effect on survival, b) the use of the Mantel-Haenszel procedure was inappropriate for the purpose for which it was used. A survey of the available evidence fails to substatiate the claim that the immunological system effects of local irradiation relate in any way to decreased survival. Recommendations for the use of irradiation postoperatively in the treatment of breast cancer are made.
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Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cytotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written.
The effect of 5-thio-D-glucose on the viability and radiosensitivity of P815-X2 mouse mastocytoma cells was studied in vitro. By itself, this compound is specifically cytotoxic toward hypoxic cells; moreover, it sensitizes hypoxic cells to irradiation while it protects aerobic cells from radiation damage. These features, together with its low toxicity, suggest that 5- thio-D-glucose may be useful adjuvant to radiotherapy
The effect of different parameters on dose distribution in electron-beam arc therapy was studied in order to develop a technique for routine clinical use. A special diaphragm was designed to facilitate telecentric rotation. Dosimetry was performed with an ion chamber, film, and LiF powder in cylindrical polystyrene phantoms and an Alderson Rando phantom. Dose distributions were evaluated with regard to dose homogeneity, and a method of sharpening the dose fall-off near the ends of the arc was proposed. Criteria for selection of isocenter depth and field size were developed. Methods of dose calculation, calibration, and treatment planning are discussed.
This study compares the effects of fractionated 2400, 4800 and 7200 rad doses of Co-60 irradiation on the formed and developing teeth of the rats. The 7200 rad dosage was found to cause damage to both odontoblasts and ameloblasts of developing incisors but to spare previously formed molars.
Lymphography of 123 newly diagnosed patients with lymphoma was followed by staging laparotomy without intra-operative abdominal roentgenography. These patients were retrospectively evaluated for residual abnormal nodes with postoperative abdominal roentgenography. Sixteen patients with pathologically normal nodes at laparotomy had residual lymphographically abnormal nodes at postoperative roentgenography. Nine patients received less extensive irradiation than they would have if the remaining abnormal nodes had been biopsied and found to contain tumor. Two had shortened survivals as an apparent consequence.
5-Thio-D-glucose effectively killed hypoxic mastocytoma cells of DBA/2J mice, whereas it merely suppressed the growth of oxic cells. This specific toxicity suggested that 5-thio-D-glucose may be a useful adjuvant to radiotherapy by eliminating hypoxic protection.