Clinical relevance of the CA-125 assay for the management of patients with ovarian carcinoma.
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Biomedical subjects
Publications and source records attributed to J P Concannon.
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From August 1978 through December 1979, 51 patients with advanced non-oat cell carcinoma of the lung were enrolled in a Phase I/II trial sponsored by the Radiation Therapy Oncology Group (RTOG) employing misonidazole (a 2-nitroimidazole) as a hypoxic cell sensitizer and radiation. The purpose of this study was to test drug and radiation tolerance and to assess the short term efficacy of this unconventional treatment. Tumor doses of 600 rad wer given twice weekly for three weeks for a total of 3600 rad, preceded four to six hours by misonidazole in a dose of 2 gm/m2 or 1.75 gm/m2, administered orally. Forty-nine patients were evaluable. Serious toxicity from this treatment was rare. Grade 2 or 3 peripheral neuro-toxicity occurred in eight of 24 patients (33%) with drug doses of 2 gm/m2 and in four of 26 patients (15%) who received 1.75 gm/m2. Grade 3 or 4 central nervous system toxicity occurred in two patients. Two patients developed serious late radiation complications: one patient had a transverse myelitis that appeared one year following delivery of 3600 rad to the spinal cord; a second patient developed a tracheoesophageal fistula and pericarditis eight months following treatment. Objective responses were reported in 67% of patients (complete in 18%); 70% of the patients died with a median survival time of nine months. Of 32 patients eligible for 12 month follow-up, 34% survived more than one year. Patterns of relapse after initial treatment and comparison with results from other RTOG trials using conventional fractionation are discussed.
A clinical study to evaluate the Makari Intradermal Test (MIT) involved 180 patients seen with symptoms suggestive of malignant disease, 85 of whom were subsequently shown to have carcinoma of the large bowel, and 66 asymptomatic volunteers. The prognostic value of initial and serial studies relative to patient-survival rate and the efficacy of serial studies in detecting disease in long-term follow-up of patients with resected malignant lesions were evaluated. On the basis of this study, the MIT appears to merit further investigation, not as a definitive diagnostic procedure, but as a survey for identifying patients with early malignancy or individuals at high risk to malignant epigenesis.
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The general immune competence of 146 patients with bronchogenic carcinoma was measured, prior to irradiation therapy, by determining dinitrochlorobenzene (DNCB) reactivity, delayed cutaneous hypersensitivity (DCH) response to microbial antigens, peripheral lymphocyte counts, peripheral T and B lymphocyte counts, and the response of patient's lymphocytes to stimulation by phytohemagglutinin (PHA), concanavallin A (Con A) and pokeweed mitogen (PWM). Analyses were performed by the life-table method to determine the correlation of the immune status of these patients with survival rates. Statistically significant differences in survival were noted between the groups of patients with normal values when compared with the patients with abnormal values for the majority of the tests of general immunity. A stage of disease correlation with survival rate was noted for all groups of patients with abnormal immune measurements, but it was absent for many of the immune parameters when patients with normal values were compared. The effects of histology, age, and sex did not appear to influence the survival data as significantly as did the immune status of the patient. These data indicate that measurements of general immune competence may be of significant prognostic value for the management of patients with bronchogenic carcinoma. The measurement of DNCB reactivity shows the strongest correlation with survival rate.
The responses of lymphocytes to stimulation by three common plant mitogens (PHA, Con A, and PWM) have been studied prior to irradiation treatment in 65 patients with bronchogenic carcinoma. The lymphocyte mitogen stimulation (LMS) responses of these patients were determined to be normal or abnormal based on data obtained from similar studies in healthy volunteers. The data for the patients with lung cancer were analyzed for correlations between the lymphocyte responses and (1) the stage of disease, (2) prognostic significance, and (3) period of survival. Statistically significant correlations were observed between the responses of lymphocytes and the stage of disease and the period of survival. However, this study indicates that these correlated responses will be of limited prognostic clinical value for individual patients.
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We have drawn upon the work of numerous investigators to formulate a model describing the principles governing the acute response of the intestinal epithelium to cytotoxic agents. Tolerance (exposure required to kill 50 per cent of the animals) to abdomen-only irradiation was measured experimentally in the mouse using a total of 17 time/dose fractionation schedules. The principle determinants of intestinal response to fractionated radiation therapy were magnitude of each fraction and the introduction of regular recovery intervals during the course of treatment. The roles of exposure per week, exposures per day, and radiation days per week were also examined. The log-log plots of endpoint v. either number of fractions or overall treatment time yielded straight lines with slopes of 0 with 54 and 0 with 59 and y intercepts of 1,270 and 812 rets respectively. The single dose for 50 per cent acute intestinallethality (LD50/6 days) was 1,610 R. It would appear that the acute intestinal tolerance to fractionated irradiation is, in the mouse, extremely dependent upon fraction number and overall treatment time. The biological basis for intestinal tolerance to cytotoxic agents is discussed in light of the results of these studies and the model initially described.
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