Milton H. Dalbow

Prognostic value of preoperative carcinoembryonic antigen (CEA) plasma levels in patients with bronchogenic carcinoma

Preoperative plasma CEA levels were measured by radioimmunoassay for 149 patients with bronchogenic carcinoma. The data were used to determine the prognostic value of the CEA assay in these patients. The relationship of preoperative CEA levels with stage of disease, histology and resectability was also examined. All of the patients with CEA levels >6 ng/ml died in less than 3 years while all of the patients who survived 3 to 5 years had preoperative CEA levels ≤ 6 ng/ml. The CEA assay had no prognostic significance for patients with undifferentiated large or small cell carcinomas since all of the patients with undifferentiated large cell carcinoma had CEA levels ≤ 6.0 ng/ml and all of the patients with small cell carcinoma have died regardless of their initial preoperative plasma CEA value. The number of patients in these two histologic groups was small and perhaps the study of additional patients will show a critical CEA level for these patients as well. There was no correlation observed between CEA levels ≤ 6 ng/ml vs. >6 ng/ml and resectability of the primary tumor.

The carcinoembryonic antigen assay in bronchogenic carcinoma

Pretreatment levels of plasma carcinoembryonic antigen (CEA) were determined for a series of patients with bronchogenic carcinoma and for a series of patients with benign pulmonary disease. These data were analyzed to determine the diagnostic and prognostic value of the CEA radioimmunoassay in bronchogenic carcinoma. CEA plasma values in patients with benign pulmonary disease indicate that the level of discrimination between positive and negative tests for bronchogenic carcinoma should be at least 5.0 ng/ml. Half the patients with bronchogenic carcinoma in this study had CEA plasma values less than 5.0 ng/ml. The data also indicate that the CEA test does not correlate well with patient survival or stage of disease at time of diagnosis, and that the CEA test frequently fails to identify patients with extensive metastatic disease. It is concluded that the pretherapy plasma CEA level will not be of value as a diagnostic or prognostic test in the management of a significant number of patients with bronchogenic carcinoma.

Clinical significance of the preoperative plasma carcinoembryonic antigen (CEA) level in patients with carcinoma of the large bowel

Preoperative levels of perchloric acid extractable plasma CEA were measured in 911 patients with complaints of the digestive system. A final diagnosis of benign disease was made for 579 patients; 332 patients were found to have cancer. Data for the preoperative CEA values were examined for clinical significance as an aide to diagnosis, preoperative disease staging, and prognosis.The results of our analysis support the conclusions of many investigators that the CEA assay is not a clinically useful diagnostic test, but it shows limited value in preoperative staging and a somewhat stronger correlation with prognosis.

Adjuvant specific active lung cancer immunotherapy trials. Tumor-associated antigens.

The 10‐year cumulative experiences of five year survivals of patients entered into a successful phase II specific active tumor‐associated antigen (TAA) immunotherapy trial, a successful phase III specific active immunotherapy trial A and of patients from centers with acceptable protocol violation levels of an unsuccessful specific active immunotherapy trial B are evaluated. Here the authors report the efficacy of specific active TAA immunotherapy when the protocol is adhered to strictly, where the induction of cell‐mediated immunity to TAA indicated a successful adherence to the protocol rather than the strategic result when centers from the third trial with major violations are included. The authors repeat here a summary of each of the three separate trials, each of the three trials having been reported elsewhere in their entirety, so that these total results may be compared to the present analysis. The survival experiences of a total of 234 lung cancer Stage I and Stage II patients, including all violations, from centers in northern New York, northern New Jersey, western Pennsylvania and eastern Canada show a statistically valid (P = 0.0002) 5‐year survival difference between the control groups (receiving adjuvant alone or no treatment) at 49% survival and the specific active immunotherapy groups at 69% survival. The best promise of specific active immunotherapy alone in an adjunctive treatment setting is with early stage lung cancer. In addition to tests which monitor the effect of TAA immunotherapy induction of long‐lasting cell‐mediated immunity, tests (monoclonal antibody‐derived epitope enzyme immunoassays) were developed to monitor specific, early antibody rises in the bloodstream (circulating humoral immunity).

Carcinoembryonic Antigen (CEA) Plasma Levels in Untreated Cancer Patients and Patients with Metastatic Disease

Radioimmunoassays for determination of carcinoembryonic antigen (CEA) were performed on plasma samples from previously diagnosed but untreated cancer patients, cancer patients with metastatic disease, control groups with non-neoplastic disease, and healthy volunteers. The CEA radioirnmunoassay failed to detect 34% of those with active cancer, raising questions about the diagnostic significance and value of the CEA assay as a screening procedure for detection of cancer.

Correlation of Serum Immunoglobulin E Elevations with Clinical Stages of Dysthyroid Orbitopathy

Total immunoglobulin E (IgE) was measured by an enzyme-linked immunoassay in serum samples from patients with dysthyroid orbitopathy and from a group of healthy volunteers. All the serum donors had no symptoms of allergy or infection and were not given any immunoregulative treatments for at least 6 months before the sampling. One hundred thirty-seven dysthyroid orbitopathy patients were rated clinically as belonging to one of the following groups: (1) stable dysthyroid orbitopathy; (2) active dysthyroid orbitopathy; (3) chronic or recurrent dysthyroid orbitopathy; or (4) dysthyroid orbitopathy characterized by limited myopathy. The serum IgE levels of all these groups were compared with 26 healthy, nonatopic volunteers. The mean IgE levels of groups 3 and 4 were significantly higher than the mean IgE level of the control group as well as that of the group with stable dysthyroid orbitopathy. Furthermore, serial readings on several patients were consistent with the hypothesis that serum IgE is elevated in connection with certain stages of rapid dysthyroid orbitopathy progression and also with two unusual clinical forms of dysthyroid orbitopathy.

Radiation and actinomycin D mortality studies in C57BL/6 MICE. II. Combined treatment and gastrointestinal lethality

C57BL/6 mice were treated with actinomycin or radiation therapy and with a combination of the two agents. LD50 estimates based on radiation doses were calculated from 6‐day (intestinal death) mortality data. A factorial analysis of the data was performed to determine the. main effects for actinomycin (A) or radiation exposure (R) as well as actinomycin‐radiation (AR) interactions. The LD50 data indicated that the effects of the combined treatment were generally more lethal in causing intestinal death than the effects of either agent given independently. Significant main effects for A and R were generally observed with few AR interactions. The principal mechanism for intestinal death in animals treated with various combinations of actinomycin and radiation exposure appears to be additive cytotoxicity either at the level of crypt survival and/or prolongation of the time to the appearance of the compensatory proliferative response.

Immunoprofile studies for patients with bronchogenic carcinoma—I correlation of pre-therapy studies with stage of diseases

Multiple parameters that contribute to the general immune competence were measured for 145 patients with bronchogenic carcinoma. These same parameters were measured for a group of healthy individuals to establish normal values for each of the tests of immunity. The immunoprofile data for the patients were analyzed on the basis of normal or abnormal measurements to determine the effects of stage of disease, histology, prior surgery and age of the patients on the immune system. A strong stage related correlation with immune impairment was observed in that an increased number of patients with perturbed immunity could be demonstrated for many of the parameters studied.

Mitogenic augmentation of T cells from immunodepressed cancer patients by a murine interleukin-1 (IL-1).

An interleukin-1 (IL-1) lymphocyte-activating factor, with an approximate molecular weight of 13,000-16,000 was isolated from the culture supernatants of a murine macrophage-like cell line, P388D1. Contrary to the general belief that murine mediator is incapable of stimulating human lymphocyte mitogenic responses, leukoagglutinin (LA)-induced mitogenesis of peripheral blood lymphocyte (PBL) were significantly affected by murine IL-1. On one hand, when PBL were obtained from either normal healthy individuals or from cancer patients who still possessed normal levels of general immunocompetence, their mitogenic responses were not augmented any further by the murine mediator. Instead, slight but significant suppression were noted in most cases. On the other hand, the LA-induced responses of PBL from 5 immunodepressed cancer patients were markedly augmented by murine IL-1.

Clinical evaluation of the Makari intradermal test in patients with cancer of the colon and rectum

A clinical study to evaluate the Makari Intradermal Test (MIT) involved 180 patients seen with sympotoms 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.