Meryl Gale

Hostility, risk of coronary heart disease, and mortality

&NA; Level of hostility (Ho) was assessed by a 50‐item subscale of the Minnesota Multiphasic Personality Inventory at the initial examination of 1877 employed middle‐aged men who were free of coronary heart disease (CHD). Ten‐year incidence of major CHD events (myocardial infarction and CHD death) was lowest in the first quintile of the Ho scales distribution, highest in the middle quintile, and intermediate in the other three quintiles. After adjustment for age, blood pressure, serum cholesterol level, cigarette smoking, and intake of ethanol, the relative odds of a major CHD event was 0.68 for men with Ho scores less than or equal to 10 points in comparison to men with higher scores. The Ho scale was positively associated with crude 20‐year mortality from CHD, malignant neoplasms, and causes other than cardiovascular—renal diseases and malignant neoplasms. After adjustment for the risk factors listed above, the Ho scale had a statistically significant, positive, monotonic association with 20‐year risk of death from all causes combined. A difference of 23 points on the Ho scale, i.e., the difference between the means of the first and the fifth quintiles, was associated with a 42% increase in the risk of death. These results support the previous findings of Williams et al. with respect to the Ho scale and coronary atherosclerosis, and also suggest that the Ho scale may be associated with factors having broad effects on survival.

Type A score (Jenkins activity Survey) and risk of recurrent coronary heart disease in the aspirin myocardial infarction study

The Jenkins Activity Survey (JAS), a questionnaire developed to assess the type A behavior pattern, was administered to 2,314 participants in the Aspirin Myocardial Infarction Study. All had a myocardial infarction (MI) before entering the study and were followed for at least 3 years. The JAS type A score was not significantly related to risk of recurrent major coronary events (definite nonfatal MI and coronary death) in the group of 244 women, the group of 2,070 men, or the subgroup of 671 men who were employed full-time in professional, technical or managerial positions. These results indicate that the JAS type A score is not useful in assessing prognosis after MI. By inference, traits measured by the JAS type A score, such as competitiveness, orientation toward achievement and preference for a rapid pace of life, appear not to be associated with increased risk of recurrent major coronary events.

Pre-treatment prognostic factors in stage III non-small cell lung cancer patients receiving combined modality treatment

Approximately one-third of non-small cell lung cancer (NSCLC) patients present with locally advanced disease. Increasing numbers of clinical trials are being conducted in this group of patients and recently a new international staging system has been introduced, resulting in the sub-division of Stage III into IIIa (potentially operable disease) and IIIb (inoperable disease). Kaplan-Meier survival analyses and Cox regression analyses were used to analyze data from 129 Stage III NSCLC patients who had been treated on two consecutive Phase II trials testing combined modality treatment. The pretreatment characteristics of these patients were: median age--59 years, males/females--87/42, caucasian/non-caucasian--111/18, squamous cell or adenocarcinoma/large cell carcinoma--57/72, previous weight loss less than or equal to 5%/greater than 5%-76/46, previous history of cardiorespiratory disease--no/yes--91/36, performance status (PS) 0-1/2-3--102/27, Stage III, 2 groups--IIIa/IIIb--83/46, Stage III, 3 groups--IIIa T3 N0/IIIa N2/IIIb--41/41/47, surgical eligibility--eligible/ineligible--83/46. Kaplan-Meier statistics revealed significantly longer survival for PS 0-1 versus 2-3 (p = .001), for eligible versus ineligible for surgery (p = .003), for Stage-IIIa versus IIIb (p = .004), and for Stage-IIIa T3N0 versus IIIa N2 versus IIIb (p = .004). The best model developed from Cox regression analyses included stage (IIIa T3 N0 vs IIIa N2 vs IIIb), PS, and sex. These observations appear to have implications for clinical research in Stage III NSCLC.

The prognostic value of chromosome 7 polysomy in non-small cell lung cancer patients treated with gefitinib.

Introduction: Specific subpopulations of non-small cell lung cancer (NSCLC) patients defined by clinical features and molecular profiles seem to derive greater benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, but no general consensus on molecular testing to optimize treatment has emerged. The objective of this study was to evaluate chromosome 7 polysomy and other potential indicators of gefitinib efficacy in advanced NSCLC patients. Methods: Paraffin-embedded tumors from 82 patients treated with gefitinib were analyzed by immunohistochemistry for expression of EGFR and other markers, and by fluorescence in situ hybridization for EGFR gene or chromosome copy number. Mutational status was assessed by single-strand conformational polymorphism, sequence-specific polymerase chain reaction, and direct sequencing. Molecular and clinical characteristics were evaluated in relation to objective response (OR), progression-free survival (PFS), and overall survival (OS). Results: EGFR mutational status (p = 0.002), never smoking (p = 0.052), and chromosome 7 polysomy (p = 0.029) were significant indicators of OR. EGFR mutation, pAKT or PTEN expression, and chromosome 7 polysomy were associated with longer OS. There was a significant difference in OS between the chromosome 7 polysomy groups (p = 0.015) and the groups with both chromosome 7 polysomy and pAkt+ (p = 0.002) and both chromosome7 polysomy and PTEN+ (p = 0.04). In a stepwise proportional hazards analysis, chromosome 7 polysomy and PTEN+ expression were both significantly associated with longer OS (p = 0.004 and 0.017 respectively). Conclusion: These results suggest that further study of chromosome 7 polysomy and of pAKT and PTEN expression in patients treated with EGFR tyrosine kinase inhibitors is warranted in developing a clinical test for selecting patients for gefitinib therapy.

Combined modality therapy for stage III non-small cell lung carcinoma : results of treatment and patterns of failure

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Lukes Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.