Bone marrow chromosome abnormalities in breast cancer in patients following adjuvant chemotherapy.

Two patients developed acute bone marrow cancer following mastectomy and institution of alkylating agents as adjuvant chemotherapy. An aneuploid condition was observed in both cases, along with involvement of chromosomes 11 and 12 in structural rearrangements. Subsequent studies of 18 patients who had or had not received such therapy showed no evidence of chromosomal aberrations. However, the long-term effect of adjuvant chemotherapy in cancer patients is still of concern until additional information becomes available.

Pericardial effusions in patients with malignant diseases.

Six consecutive patients with malignant disease who developed a pericardial effusion were successfully treated with a single pericardiocentesis (two patients) or with indwelling pericardial cather drainage (four patients). There were no complications in either group. Short-term catheter drainage appears to be a safe and effective alternative to surgical establishment of a pericardial window.

Erythema annulare centrifugum and Hodgkin's disease: association with disease activity.

The skin lesions of erythema annulare centrifugum developed in a 58-year-old woman who had Hodgkin's disease. Response of the neoplasm to vinblastine sulfate was accompanied by disappearance of the skin lesions. When therapy was discontinued, both disorders recurred, and both responded to reinstitution of vinblastine therapy. To our knowledge, this case is the first reported association of erythema annulare centrifugum and Hodgkin's disease. The cutaneous manifestation in this patient were a nonneoplastic concomitant of her neoplastic disorder.

Leucovorin in combination chemotherapy of breast cancer.

Cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone were administered for 165, 28-day cycles to 33 patients with metastatic breast cancer. Because of serious infections (fever larger than or equal to 101 degrees F. granulocytes less than 1,000/mm, 3 and hospitalization) and 1 drug death in the first 4 patients, oral calcium leucovorin, 20 to 30 mg/m2 orally, was given 2 days after methotrexate in subsequent treatment cycles. There were 26 cycles without calcium leucovorin and 6 serious infections; 139 cycles with calcium leucovorin and 5 serious infections (p = 0.002). Objective response was seen in 13 of 18 evaluable patients with no previous treatment and in only 2 of 11 patients with previous treatment (p = 0.0065). Equivalent doses were given to all subsets of patients. It is concluded that leucovorin added to the above combination of drugs can preserve antitumor activity while decreasing serious infections and that prior therapy significantly decreases the response rate to this combination.

Clinical usefulness and reproducibility of histologic subclassification of advanced diffuse histiocytic lymphoma.

Thirty-one patients with stage III and IV diffuse histiocytic lymphoma (DHL) were treated uniformly with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP). The patients were subclassified independently by two hematopathologists into groups with predominantly large noncleaved cells (eight patients), predominantly large cleaved cells (seven patients), a mixture of large cleaved cells and large noncleaved cells (11 patients), tumors with the characteristics of immunoblastic sarcomas (two patients) and unclassified (three patients). The concurrence rate on applying the subclassification was 85 per cent. Survival in patients with large noncleaved cells was superior to that of the other patients as a group (p less than 0.001), and to that of those with large cleaved cells (p less than 0.05) and large cleaved and large noncleaved cells (p less than 0.025). All the patients with large noncleaved cells are alive and "off" therapy without evidence of progressive disease. This histologic subclassification seems to identify a subgroup of patients with advanced diffuse histiocytic lymphoma having large noncleaved cells who have an excellent prognosis when treated with CHOP.

Multimodality therapy of favorable prognosis non-Hodgkin's lymphoma.

Twenty-seven previously untreated patients with favorable prognosis non-Hodgkin's lymphoma were treated with a combination of total body irradiation followed by cyclophosphamide - vincristine - prednisone (CVP). The dose of total body irradiation was planned to be 150 rad followed by 6 cycles of chemotherapy. The complete response rate was 59%; the complete plus partial response rate, 93%. The 50% disease-free survival was 8 months. The actuarial projected 5 year survival was 60% and the disease-free survival at 5 years was 27%. The program was well tolerated by the majority of patients. It is possible for some patients with favorable non-Hodgkin's lymphomas to achieve prolonged periods of disease-free survival when treated with combinations of irradiation plus chemotherapy.

Reasons for failure of MOPP to cure Hodgkin's disease: The importance of dose and schedule.

Thirty-six patients with advanced Hodgkin's disease who were treated primarily with MOPP were evaluated to determine the reasons for MOPP failure. Complete remission was achieved in 22 (61%) of the patients, and the predicted 5-year survival rate for all patients is 60%. Reasons for the failure of MOPP to cure patients in this series included: 1) Idiosyncratic drug reactions in 2 patients (6%). MOPP was discontinued after one cycle because of drug-related hepatitis or skin rash; 2) Resistant disease in 8 patients (22%). Primary treatment failure was significantly associated with the presence of B symptoms (p = .005) and age greater than 40 years (p = .02); 3) Death from complicating infection in 5 patients (14%). Four patients died without evidence of Hodgkin's disease while responding to MOPP from pneumocystis pneumonia, viral pneumonia, bacterial pneumonia, or bacterial septicemia. One patient died in complete remission from sudden, overwhelming sepsis; 4) Relapse from complete remission in 4 patients (11%). All patients who relapsed had deviations from the planned dose or timing of MOPP. Remission duration was shorter (p = .06) in patients with documented deviations in MOPP administration than in patients without such changes. It appears that new treatment approaches are needed for patients with B symptoms, and that failure to deliver MOPP on schedule in the planned dose increases the risk of relapse.

A decision-analysis methodology for consideration of morbidity factors in clinical decision-making.

An explicit and systematic means of incorporation of good medical practice plus individual patient preferences (utilities) for pretreatment and treatment options for a serious but curable neoplastic disease has been investigated. The methodology allows important quality-of-life information to be transmitted to patients, with the goal of providing an improved basis for informed consent. The example of Hodgkin's lymphoma staging and treatment selection is used. Individual patient utilities can be expressed and incorporated into a formal decision analysis for those who face the option of selecting MOPP chemotherapy or of pursuing the staging process in order to obtain a chance of being treated appropriately with irradiation. Equal survival probabilities for the two options are assumed, thus the short- and long-term toxicities (quality of Life) are the determinants of the decision. Patient-derived utilities can be developed for the 15 categories of anticipated toxicity. This, together with probabilistic inputs regarding toxicity severity and duration, will yield expected utilities for each of the decision options. Three physicians were studied and evaluated in the role of a patient. The physicians' toxicity preferences were different and because of this the management option of choice was different for each. This methodology allows explicit patient preferences to be incorporated into medical decisions without the requirement for detailed patient understanding of testing and/or treatment morbidity frequency and severity.

Comparison of treatments for symptomatic Hodgkin's lymphoma employing decision analysis.

A decision analysis methodology has been developed for addressing a comparison of immediate MOPP chemotherapy without staging to staging followed by medically indicated chemotherapy (MOPP) or radiotherapy (XRT). The patients would have symptomatic Hodgkin's lymphoma. Each test and therapy was previously described in terms of 15 toxicity categories. Each was assigned a probability of the occurrence over the five grades of toxicity. Each grade was assigned an expected duration of the toxicity for each test or therapy. Both actual probabilities and judgmental probabilities were used. Utilities for the 15 toxicity categories were solicited. The staging-test-morbidity outcomes only pertained to decision paths which were directed at a chance to receive XRT as the medically dictated therapy. Relative scalar weights were assigned to each grade IV toxicity of zero utility by three physicians. An additive (linear) model was used to compute composite utilities for the paths. There were three different outcomes for these individuals in the initial analysis: 1) MOPP immediately without staging; 2) MOPP immediately or if staging had proceeded to a negative bone marrow then further staging was preferred; and 3) Staging in order to have any change to receive XRT. When a lower toxicity program of presumed equal efficacy was substituted (ChlVPP) the decision changed so that all three participants now would receive ChlVPP instead of staging based on their personal preferences about morbidity outcomes. Decision analysis can contribute to selection between treatments based on differences in an individual's preferences in regard to varying degrees and spectra of toxicity.

The introduction of ambulatory electrocardiographic monitoring for the diagnosis and management of myocardial ischemia.

We report on the introduction of a new technology and a new method for the management of chronic coronary artery disease into a managed care environment. The introduction incurred substantial resistance from subspecialty consultants, primary care physicians, and top management. Strategies were developed to overcome these resistances. Modification of the program as well as the development of incentives occurred. These measures continue to evolve. The program, to date, has achieved approximately 50% penetration. The demonstration of better health outcomes and financial savings will almost certainly temper the resistance encountered from all three groups identified.

Hepatic scan defects following radiotherapy for lymphoma.

Twenty-one patients with lymphoma were evaluated for the presence of hepatic scan defects following radiotherapy to fields which included the left lobe of the liver. Two distinct patterns of hepatic scan defects were noted: (a) a radiation port defect (Type I), and (b) attenuation of the left lobe (Type II). Five of seven patients evaluated within six weeks after radiotherapy demonstrated Type I defects but all seven subsequently developed Type II defects. Seventeen of the 21 patients developed Type II defects which have persisted (follow-up, up to 66 months). These characteristic defects should not be confused with other causes of hepatic scan defects in evaluating patients with lymphoma. The defects occur in a high percentage of patients and may persist for long periods.

Veteran's health care: time for a change?

The Department of Veterans Affairs' mission is "to care for him who are shall have borne the battle for his widow and orphan." The Veterans Health Administration comprises 172 hospitals that are the hub of the health care delivery system. It is the largest provider of graduate medical education, and one of the major research organizations in the United States. The medical care budget exceeds $17 billion annually. Most of the persons cared for are not legally entitled to this health care based on service connected disability. The utilization of acute care hospital beds appears excessive when compared to that obtainable with managed care for Medicare or commercial insurance beneficiaries--the cost per member per month is three times higher. There may also be exploitation of the Veterans Administration hospitals by university medical schools. The Veterans Health Administration is a very expensive way to deliver care to entitled service connected veterans. Therefore, it is suggested that privatization be considered as an alternative vehicle for delivering health care.