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Title: Immunological investigations and immunotherapy in lung cancer
Author: Stack, B. H. R.
ISNI:       0000 0001 3476 5624
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1982
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This thesis examines the value of immunological methods in the treatment, diagnosis and assessment of prognosis of lung cancer. Delayed hypersensitivity skin tests and laboratory tests of immunological function were performed in patients with operable lung cancer who were then randomly allocated to the autograft or non-autograft groups. In a pilot trial in 15 patients, the autograft group received intradermal injections of autologous irradiated tumour cells and BCG. during three weeks after operation. In this trial only, both groups of patients were given radiotherapy to the mediastinum three weeks after operation. In the subsequent main trial in 83 patients, both groups received one pre? operative percutaneous injection of BCG. The autograft group only were given serial injections of autologous irradiated tumour cells and percutaneous BCG. during the three weeks after operation. While the prevalence of positive tuberculin tests among the lung cancer patients before operation was similar to that of controls, sensitisation after challenge by DNCB. was less common in the lung cancer patients, suggesting that there is some impairment of the afferent limb of the immunological response in this condition. Lymphocyte transformation by PPD. but not PHA. or pokeweed mitogen was depressed. Relative depression of certain immunological tests was seen in patients with more advanced disease and a poorer prognosis (total lymphocytes, DNCB.reactivity) and in squamous cell carcinoma (tuberculin test). The main immunological effect of postoperative immunotherapy was a prolonged increase in tuberculin reactivity. By constructing actuarial life table curves for survival and duration of freedom from tumour recurrence and by measuring the median times for these, it was shown that DNCB. positive autograft group patients and those with stage I tumours had better clinical results than non-autograft patients (p = 0.02 to p = 0.09)? Although a higher proportion of stage I patients in the autograft group survived free of tumour recurrence two years after operation, the difference was not statistically significant. Adjuvant specific autologous immunotherapy thus seemed, at best, to have only a weak therapeutic action in operable lung cancer. In a separate study, circulating levels of tumour markers in unselected lung cancer patients were compared with those of control patients with benign pulmonary disease. Elevated levels of carcinoembryonic antigen (CEA.) were found in 17%? of pregnancy-associated a^-glycoprotein (a^-PAG.) in 16%, of casein in 1 b?/o, of human chorionic gonadotrophin in 6?/o and of a-foetoprotein in 1.5%? CEA. levels were higher in patients with extensive disease (23%) ? There was discordance between raised levels of CEA. and a^-PAG. Elevated levels of one or more markers were found in kG'/o of patients in whom four or more markers were measured. In a different series of unselected lung cancer patients, circulating levels of immunoreactive ACTH. were raised in 2k?/o of patients with small cell carcinoma but only in 3?/? of patients with non-small cell carcinoma. Elevated levels were commoner in small cell carcinoma patients with extensive disease. The results showed that when the upper limit of "normal" was that of patients with benign pulmonary disease, the prevalence of elevated levels of tumour markers was much lower than that claimed by other authors. Hence measurement of these markers is of little or no diagnostic value in lung cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine