Robert K. Oldham

Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group.

The authors present prognostic information on recurrence and survival for resected Stage I lung cancer patients with squamous cell carcinoma, adenocarcinoma or large cell carcinoma. The data derive from 392 carefully staged patients and include results from the history and physical examination, preoperative laboratory tests, nature of the surgery, complications, initial pathologic findings following surgical resection, and final pathologic review. A simple multivariate model of recurrence, which is used to classify patients into low, intermediate, and high‐risk groups, is based on tumor size and location (T1, T2), histologic type (squamous, nonsquamous/mixed) and nodal status (N0, N1). To model survival, the performance status and the presence of empyema, pneumonia, or wound infection were added to the previous factors. Not all factors associated with increased mortality are associated with increased risk of recurrence, and, in particular, postoperative empyema, pneumonia or wound infections carry an increased risk of death only. Serial measurements of performance status and leukocyte count have the potential for monitoring for increased risk of recurrence and death.

Endodermal sinus tumor of the mediastinum

Endodermal sinus tumor (EST) of the mediastinum is a rare germ‐cell neoplasm affecting mainly young adult males. Ten patients with EST were treated with a multimodality approach that included surgery, chemotherapy, and radiotherapy. All patients had relapses after achieving a transient response except one who is still in complete remission more than five years following the diagnosis of the disease. Optimal therapy for this neoplasm has yet to be discovered. The disease is a subset of extragonadal germ cell tumors which appears to be lethal in most cases, particularly when the primary tumor is unresectable. The first case of five‐year disease‐free survival is described.

Human natural cell-mediated cytotoxicity

SummaryNatural cell-mediated cytotoxicity has been shown to be age-dependent in both rats and mice. The present study was undertaken to study age-related levels of natural cytotoxicity in humans. Mononuclear peripheral blood cells from over 200 normal volunteers were co-incubated with 51Cr-labeled K-562 for 4 h and the supernatants assayed for released isotope. No striking age-related variations in natural cytotoxicity were observed. Cord blood was shown to exhibit both high and low levels of natural cell-mediated cytotoxicity. There was no significant difference in the levels of natural cytotoxicity between males and females. Thoracic duct lymphocytes (TDL) from prospective kidney graft recipients were tested for natural cytotoxicity at intervals during drainage. Natural cytotoxic activity was undetectable in samples from initial drainage but increased as the drainage progressed. This increased activity was correlated with decreased in vitro responsiveness to PHA and decreased levels of E-rosettes in these TDL.

Carcinoma of the lung: Immunotherapy with intradermal BCG and allogeneic tumor cells

Abstract After lobectomy or pneumonectomy 45 patients with stage I and 6 with stage II non-small cell carcinoma of the lung were randomized to receive: no further therapy; intradermal BCG; or BCG plus allogeneic irradiated tumor cells intra-dermally twice monthly for 24 months. Patients were observed for 2–51 months at this writing. The homogeneity of the disease free interval (DFI) (i.e., differences in the pattern of relapses) was tested for the three groups. Analysis indicated signifance at the p −0.062 level comparing DFI from control to BCG treated patients to BCG + cells treated patients; a difference also was found when the control group was compared with the combined immunotherapy treated groups ( p = 0.061). When only patients with stage I disease were analyzed by trend analysis this difference was magnified in favor of the immunotherapy treated patients ( p = 0.027); analysis of the T 1 NoMo only groups revealed a similar result ( p = 0.042). No significant differences were seen when data were analyzed for survival. Moderately severe local inflammatory reactions occurred in 43% of patients who received BCG immunotherapy, requiring reduction in frequency of its administration. There were no adverse effects from the administration of allogeneic tumor cells. Pasteur BCC may prolong DFI in resectable lung cancer and warrants further investigation in clinical trials.

Early side effects of intrathoracic BCG therapy in patients with stage I squamous cell carcinoma, adenocarcinoma, or large cell lung cancer

SummaryData are presented on 179 stage I lung cancer patients subjected to resection operations and then given adjuvant intrapleural BCG and subsequent isoniazid (INH) therapy and on 167 control patients given intrapleural saline and placebo pills in a two-arm randomized double-blind study. The predominant immediate response to BCG/INH therapy was hyperpyrexia, which was found to be more pronounced in patients with larger induration in pretreatment PPD skin tests. Subsequently, chemical hepatitis (6 cases after BCG/INH versus 1 case after saline/placebo), peripheral neuropathy (3 versus 1), dermatitis/hives (5 versus 2), pleural thickening (4 versus 0), and persistent fever (10 versus 0) were noted. Analysis of laboratory changes measured at 18 weeks following randomization revealed that patients with BCG/INH lost 1.1 kg in weight and 0.30 g/dl in hemoglobin concentration on average, whereas control patients gained 1.2 kg and 0.33 g/dl, respectively. Modest rises in SGOT and alkaline phosphatase were apparent at 6 weeks after instillation of BCG compared with controls, but these differences were no longer statistically signifikant after 18 weeks. These side effects notwhithstanding, the BCG/INH therapy was well tolerated.

High-dose methotrexate with citrovorum factor rescue in non-small-cell lung cancer

SummaryNineteen patients with non-small-cell carcinoma of the lung were treated with high-dose methotrexate and leucovorin rescue. Two partial responses (10.5%) were observed, lasting 13 and 17 weeks. Toxicity was acceptable. It is concluded that the occasional benefit of high-dose methotrexate with leucovorin rescue at this dose and according to the schedule described for these patients does not warrant further study.

Immunologic monitoring and immunotherapy in Ewing's sarcoma

SummarySerial immunological monitoring was performed on 31 patients with Ewings sarcoma who were on a randomized immunotherapy trial with BCG administered by dermal scarification with a Heaf gun. Patients were skin-tested for delayed hypersensitivity reactions (DCHR) to recall antigens and extracts of tumor cells, and with keyhole limpet hemocyanin (KLH). In vitro testing consisted of lymphocyte counts, percentages of cells forming rosettes with sheep erythrocytes at 29° C and at 4° C, and leukocyte migration inhibition to tuberculin (PPD) and to 3 M KCl extracts of tumor cells. At the time of diagnosis, nearly all patients had positive DCHR to mumps and streptococcal antigens and were negative to PPD. Neither the skin tests nor the lymphocyte counts at this time gave useful prognostic information. In tests during and after therapy, the patients who responded and remained free of detectable disease had a higher incidence of DCHR to KLH and of rosette values in the normal range than did the patients who developed recurrent disease. The BCG immunotherapy had no apparent effect on immunologic parameters except for conversion of reactions to PPD.

Human tumor and normal tissue reactivity of the anti-(breast cancer) monoclonal antibody BA-Br-3 and its similarity to the anti-(epithelial membrane antigen) monoclonal antibody E29

SummaryA mouse monoclonal antibody (BA-Br-3) raised against the breast carcinoma cell line CAMA-1 was previously shown to react with a ⩾ 300-kDa globule-like glycoprotein from human milk fat also expressed in the cytoplasm and on the surface of human carcinoma cells of different histological types. In this report the reactivity of this mAb with a large number of normal and malignant human tissues was analyzed using immunoperoxidase techniques. When tested on sections of both fresh-frozen tissues and formalin-fixed, paraffin-embedded tissues, BA-Br-3 reacted with a formalin-resistant antigenic determinant expressed by normal and malignant epithelial cells. Preferential reactivity was observed at the apical portion of ductal epithelial cells in normal breast and in glandular epithelia distributed in several other organs. Reactivity with mucin-like secretions in the lumina of ducts was also found. BA-Br-3 reacted mostly in heterogenous staining patterns with 88% of 49 breast carcinoma specimens tested, regardless of their histological type or whether they were primary or secondary neoplasms. Testing of epithelial malignant tumors other than breast carcinomas with this antibody showed that 127 of 151 (84%) were also reactive. mAb BA-Br-3 and E29 (a commercially available anti-(epithelial membrane antigen) shared very similar staining patterns and distributions of reactivity with breast and other epithelial tumors. However, BA-Br-3 showed a significantly higher percentage of reactivity with melanoma (33% versus 6%,P = 0.003) and a trend toward a higher percentage of reactivity with sarcoma (55% versus 27%,P >0.05). This antibody, therefore, defines a molecule that is a member of the mucin-like epithelial membrane antigen family. Further studies are warranted to determine its usefulness in antibody-directed cancer diagnosis, prognosis, and immunotherapy.