Abstract
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.
