Predictive value of regression rates following chemotherapy of small cell carcinoma of the lung.

Tumor volumes measured at the time of initial therapy, during the 28 days following treatment, and following subsequent courses of therapy for 29 patients with small cell carcinoma of the lung were determined from serially measurable roentgenographic lesions. Tumor-halving times were calculated following initial therapy, and the proportions of pretreatment tumor volumes were evaluated within 28 days after initial therapy for 26 patients. Pretreatment tumor volumes ranged from 22.5 to 485 cu cm, with a median of 87 cu cm, a log mean of 83 cu cm, and a linear mean of 113 cu cm. The tumor-halving times ranged from 4 to 86 days, with a median of 12 days, a log mean of 12 days, and a linear mean of 16 days. The reduction of tumor volume expressed as a proportion of pretreatment volume following therapy ranged between 0.02 and 0.65, with a median value of 0.22, a log mean of 0.18, and a linear mean of 0.26. Using the linear mean of 0.26 as a discriminant for survival analysis, patients with less than 0.26 had a median duration of survival of 12 months, which was significantly longer (p = 0.035) than the median survival of 8 months for patients with greater than 0.26. Tumor-halving time of 16 days was also able to separate the survival durations of 12 months of those less than 16 days compared to 8 months for greater than 16 days (p = 0.0429). Tumor regression rate, determined from two consecutive tumor volume measurements, was correlated with the tumor volume (r = 0.677; p less than 0.0001); and volume dependency of the tumor regression rate, as specified in Gompertzian kinetics, was demonstrated.

The effects of distance from primary treatment centers on survival among patients with multiple myeloma.

Twenty-one comprehensive cancer centers participated in a national reporting system of common data items, recording information on all patients seen between 1977 and 1982. There were 240,531 patients who had data abstracted. This report describes 1,479 patients with multiple myeloma. Parameters that may effect the type of treatment given during the initial episode of therapy in the center and the effect of these characteristics on survival were studied. In the univariate analysis, age, treatment, and distance traveled to the center were statistically associated with survival. In a multivariate analysis adjusting for potentially confounding covariates, blacks survive better than whites and the effects of sex and socioeconomic status (SES) on survival approach significance. Survival consistently improved with increasing distance traveled to treatment centers. This may be a serious confounding variable in assessing the results by both single and multiinstitution clinical trials.

Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.

Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.

Sputum cytologic diagnosis of Hodgkin's disease involving the lung.

The development of pulmonary lesions during the course of Hodgkin's disease (HD) represents a diagnostic problem. Invasive studies are usually necessary to differentiate pulmonary parenchymal involvement with HD from infectious complications. A retrospective review has revealed five cases in which sputum cytodiagnosis of HD involving the lung was made. All cases were confirmed by either histopathologic examination or response to therapy. The cytology reveals a polymorphic picture with a large number of lymphoid mononuclear cells, macrophages, and unclassified cells. These cells usually have single nuclei that are lobulated and contain prominent nucleoli. Occasionally, classic Reed-Sternberg cells are present. Such evidence makes the specimen diagnostic of HD. This experience suggests that sputum cytodiagnosis may be useful adjunctive diagnostic tool in the evaluation of the conditions of patients with HD and pulmonary lesions and may make more invasive diagnostic procedures unnecessary.

Thoracic CT scanning for mediastinal Hodgkin's disease: results and therapeutic implications.

Thoracic CT scans were performed on 42 newly diagnosed patients with Hodgkin's disease. Five of 10 patients with negative chest X ray (CXR) had abnormal thoracic CT scans. Among the remaining 32 patients with mediastinal Hodgkin's disease (MHD) on CXR, pericardial (Ep) and chest wall invasion (Ec) were the two most common sites of involvement which were detectable by CT scan alone. All 14 cases with Ep had M/T greater than or equal to 0.30 and 14 of 21 with M/T greater than or equal to 0.30 had Ep. Six cases had extensive Ec. Ep and Ec accounted for 16 of 19 of the changes in treatment portal or philosophy based on CT scan findings. Because of the high risk of cardiac or pulmonary radiation toxicity in Ep or Ec, radiation treatment alone may be inadequate. Treatment of mediastinal Hodgkin's disease is reviewed here. The use of CT scans for identification of Ep, Ec, and other abnormalities will allow for more precise treatment, further define the use of conventional radiotherapy, combined modality therapy or whole lung irradiation, and allow more accurate analysis of treatment results.

An aggressive high dose cyclophosphamide and prednisone regimen for advanced multiple myeloma.

There is strong evidence that corticosteroids contribute to the objective and subjective response rate observed following treatment with several cytotoxic chemotherapy agents, and that there is a dose response effect for treatment of multiple myeloma with alkylating agents. Therefore, the Eastern Cooperative Oncology Group (ECOG) studied cyclophosphamide 600 mg/M2 given for four consecutive days intravenously combined with prednisone 100 mg orally daily in 57 patients who had progressed following or failed to respond to standard doses of these drugs. Forty eight patients met the eligibility criteria for evaluation of response and toxicity. Fourteen patients (29%) had an objective response (OR) and an additional 2 (4%) had a subjective response (SR) only. The median duration of objective response was 3.1 months and estimated median survival was 8.6 months. These results are identical to our prior experience with high dose cyclophosphamide alone. The addition of prednisone does not appear to enhance results either through increased remissions or greater survival. Therefore, this study indicates that the preferred form of high dose cyclophosphamide for multiple myeloma is as a single agent given in intravenous four day courses.

Practical applications of OCIS, a clinical information system for oncology.

The Johns Hopkins Oncology Center has developed OCIS , a computer based data system to aid medical personnel in making clinical decisions. All patients seen in the Center are entered into the system. Data is collected, analyzed and presented in formats designed to show the relationship between related clinical and laboratory data. Graphic plots are used to facilitate the detection of long and short term trends in the changing clinical status of individual patients. The system also provides major support for clinical research. An example of the use of this system is presented using data from patients with multiple myeloma.

A large private university hospital system. The Johns Hopkins Oncology Center.

Clinical trials are a major commitment for a university-based comprehensive cancer center. In 1992, The Johns Hopkins Hospital registered 3508 new patients with cancer and, from this large population, 2880 patients were entered in clinical trials (many patients participated in more than one protocol). The Oncology Center, one of many departments at Johns Hopkins that conducts clinical research, participates in phase I and II new drug trials, phase III comparative studies, and, increasingly, in epidemiologic and prevention research. This calls for much broader participation by community hospitals and for many more patients who normally would not come to Johns Hopkins for their care. There are more than 100 protocols available from the Eastern Cooperative Oncology Group, but Johns Hopkins may participate in no more than 20 at any given time. Thus, every research facility must be selective about the trials in which it participates, given the finite number of hours, dollars, and resources available to carry out these programs. The institution provides safeguards to protect the interest of the patient. These include review and annual overseeing of the concept, design, and specifics of the proposed study. The pharmacy and nursing staff play an important role in control of chemotherapy distribution and use. Patients and physicians, however, must understand the questions the study is asking and agree that they are worth answering. There are problems in motivation; information; costs to the patient, hospital, insurers, and the physician; the concept of the placebo; and informed consent. Clinical research is the most ethical way to test drugs, radiation therapy, surgical procedures, or other new treatments. The clinical trial must meet rigorous criteria of design, conduct, and analysis. The patient must understand the issues and be a volunteer. We must make every effort to help patients and physicians get information about clinical trials and to participate if they choose.

Salmonella empyema and Hodgkin's disease.

Bilateral Salmonella empyema was diagnosed in a 34-year old woman with active stage IV-B Hodgkin's disease and marked depression of immunologic function. Factors which might have predisposed to her infectious complication are discussed. The patient's dramatic response to treatment is stressed.

Displaying clinical data for decision making.

Computers are being used in increasing numbers to support health care facilities. Consequently, there is a need to examine how this technology can be effectively used to assist in the process of patient care. At the present time, most computer applications are directed toward (1) the management of large and amounts of data during a short period of time (e.g., ECG analysis and physiological monitoring) or (2) the transfer of information within a facility (e.g., Hospital Information System (HIS) order entry/results reporting). Some systems use the data for the purposes of surveillance or patient management. Other systems are concerned with the organization and presentation of the clinical data as part of the decision making process. This paper considers the ways in which systems can effectively display information. It draws upon experience with the Johns Hopkins Oncology Clinical Information System (OCIS).

Evaluation of the clinical management of cancer patients. A pilot study.

The Johns Hopkins Oncology Center, Baltimore, has carried out a pilot study of a method of data collection and analysis to be used for planning and evaluation of continuing education programs conducted in the Maryland region. This study includes definition of techniques used to prepare a test instrument that will accurately reflect actual medical practice within a hospital. The system has been field tested in three diseases, cancer of the lung, breast, and uterine cervix, in two Maryland hospitals. The system appears to be an efficient and inexpensive method for definition of decision making in specific clinical settings and for measurement of change if serial reassessment is instituted.

The Johns Hopkins Oncology Clinical Information System.

The Johns Hopkins Oncology Center has developed and maintains a clinical information system to support patient care, education, research, and administrative functions. It operates on a dedicated minicomputer (PDP-11) programmed in MUMPS. Clinical information collected includes patient medical status and laboratory values. Data are used daily in patient care and also in support of retrospective and prospective research. The use of the system to manage a large blood pheresis program and to study and treat infectious disease is described. Administrative functions include patient and personnel scheduling, program evaluation, and projects directed toward control of costs.

Intensive induction therapy for small cell carcinoma of the lung.

Fifteen patients with extensive small cell carcinoma of the lung and no prior therapy were treated with a chemotherapeutic regimen similar in intensity to the approach used in acute myelocytic leukemia. The patients received intensive induction therapy with cyclophosphamide, adriamycin, and VP-16-213 followed by treatment with a combination of BCNU, vincristine, methotrexate, and procarbazine. The objective response rate was 87% (13 of 15 patients) with three complete responses and ten partial responses. With the exception of one patient, the maximal response to therapy was achieved during therapy with the intensive cyclophosphamide, adriamycin, and VP-16-213 regimen. The three complete responders remain in remission for 159, 351, and 285 days but seven of the ten partial responders have relapsed and five of these have died. There was no unexpected morbidity associated with the intensive chemotherapy despite marked bone marrow suppression. This study demonstrates that very intensive combination chemotherapy can be safely used to achieve a high objective response rate in patients with extensive small cell carcinoma, but the complete response rate is low. An analysis of treatment failures and future directions is presented.

Transitional cell carcinoma of the bladder metastatic to the breast.

This report is the first described case of transitional cell carcinoma of the bladder metastatic to the female breast. The patient is a 42-year-old woman who underwent radical cystectomy three months prior to presentation with two asymptomatic right breast masses as the first evidence of widely metastatic bladder carcinoma. The mode of presentation is similar to that seen with other tumors metastatic to the breast and requires the clinician and pathologist to be able to distinguish this diagnosis from primary breast carcinoma.

Timed-sequential high-dose cyclophosphamide and vincristine in the treatment of multiple myeloma.

BACKGROUND: This study was designed to examine the efficacy and toxicity of high-dose cyclophosphamide (CY), and to evaluate the potential added effect of vincristine (VCR) given at a theoretic time of malignant cell stimulation in a group of patients with multiple myeloma, refractory to or relapsing after, treatment with standard doses of chemotherapy. METHODS: Patients were randomly assigned to receive CY 2400 mg per M2 as a single-day dose and VCR 1.4 mg per M2 given on Day 1 or Day 9 after the CY. RESULTS: There were 108 cases suitable for analysis. No difference in objective response (17.6%, 23.5%), subjective response, remission duration, or survival was observed in the two treatment arms. CONCLUSIONS: The authors conclude that a single, high dose of cyclophosphamide is more toxic and provides equal or less response than the equivalent dose given over 4 consecutive days and that no improved effect was detected using timed-sequential therapy with VCR.

AUTRES--the Johns Hopkins Hospital automated resume.

The Johns Hopkins Hospital has developed AUTRES, an electronic discharge summary. This computer generated report was designed to provide improved continuity in the care of patients by offering a legible, standardized summary of the events of hospitalization. It can be sent by mail, FAX, or electronically (computer-to-computer) to the next care giver who will see the patient. It is available from any network attached terminal at the hospital and School of Medicine to support re-admission to the hospital, treatment in the emergency room, or outpatient visits. AUTRES first ran in fully supported production serving the Department of Medicine in 1988. Re-engineered to take advantage of cooperative processing, it has been implemented in Neurology, Internal Medicine, Obstetrics and Gynecology and Pediatrics, with plans for phased installation in the remaining clinical departments of The Johns Hopkins Hospital.

Contribution of prednisone to the effectiveness of hexamethylmelamine in multiple myeloma.

The Eastern Cooperative Oncology Group evaluated hexamethylmelamine in 89 patients with advanced refractory or relapsing multiple myeloma. Hexamethylmelamine was initially used as a single agent administered orally at 200 mg/m2/day for the first 3 weeks of each 4-week cycle. When this regimen proved to be ineffective, it was modified first by increasing the dose of hexamethylmelamine to 280 mg/m2/day and subsequently by adding prednisone at 75 mg for the first 7 days of each 28-day cycle. None of the 39 patients receiving hexamethylmelamine without prednisone had an objective response, while two patients had minimal objective improvement (25%-50% decrease in M protein with symptomatic improvement). Only 14% of these patients had objective or symptomatic response or both. In contrast, patients treated with hexamethylmelamine plus prednisone had a 22% objective response rate, with another 14% showing lesser degrees of objective improvement. Fifty-one percent of the patients treated with this regimen had either objective or symptomatic improvement or both. Severe (grade 3) toxicity was seen in nearly two-thirds of the patients on the higher-dose hexamethylmelamine regimens compared with 37% of the patients receiving low-dose hexamethylmelamine; however, in most instances this represented rapidly reversible cytopenias. Because all but one of the patients responding to hexamethylmelamine plus prednisone had experienced previous treatment failure on regimens containing prednisone in similar dose and schedules, it is unlikely that the responses are due to prednisone alone. Instead, this study suggests that the activity of hexamethylmelamine in multiple myeloma is dependent on the concomitant administration of prednisone and that the combination regimen appears to be synergistic.

Urinary polyamines for evaluating the course of disease for patients with small cell carcinoma of the lung.

Clinical correlates with urinary excretion of polyamines were evaluated for 29 newly diagnosed and 35 previously treated patients with small cell carcinoma of the lung (SCC). The frequencies of pretreatment abnormalities were 12 (41%) for putrescine, 18 (62%) for spermidine, and 20 (69%) for spermine. In assessing disease parameters, the combined use of the abnormalities of spermidine and spermine as a discriminant was more effective than that of all three polyamines; it correlated significantly with extent of limited and extensive disease (P less than 0.001), and also resulted in significant separation of survival curves, the median survival of 11 months for both elevated compared to 19 months for neither or only one elevated (P = 0.062). No significant difference was seen in the abnormalities between no metastasis and one metastasis, whereas the frequencies of the abnormalities was highly increased in two or more metastases. The distribution of polyamines determined at regular treatment intervals showed distinctively more elevated patterns in progressive disease than in stable disease or partial and complete responses (P less than 0.01). In order to evaluate therapeutic effects on the relationship between polyamine excretion and tumor regression, correlations between urinary putrescine and spermidine were determined. The values of the ratio of spermidine to putrescine were significantly smaller in responders than in nonresponders (P less than 0.01); and these may be related to smaller tumor mass and higher tumor proliferative activity in responders, and larger tumor mass and lower tumor proliferative activity in nonresponders.