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Biomedical subjects

R Makuch

Publications and source records attributed to R Makuch.

At least 55 records · Page 3Linked to original sources
PubMed1985

Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate.

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolated CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving CNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to the CNS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Detection of pulmonary metastases in patients with osteogenic and soft-tissue sarcomas: the superiority of CT scans compared with conventional linear tomograms using dynamic analysis.

A prospective serial evaluation in 19 patients with soft-tissue and osteogenic sarcomas was performed to determine whether computerized tomography (CT) or conventional linear tomography (LT) detected pulmonary metastases earlier. Analysis of the metastatic nodules was performed radiographically with histologic confirmation by obtaining serial CTs and LTs followed by metastasectomy. Nodules were classified as stable, growing, or developing and by detection on CT and/or LT. CT was the first positive study in a significantly greater number of patients (13 CT, 1 LT; P less than .005), and CT detected the nodules earlier than LT (56 CT first v 7 LT first; P less than .0001). Ninety of 166 nodules resected were detected by CT, LT, or both (54%). The median size of metastatic nodules documented at surgical exploration and first detected by CT was significantly smaller than that first detected by LT (7.6 mm for CT v 13.2 mm for LT; P less than .05). Of 55 histologically documented metastases detected initially either by CT or LT, CT was markedly superior to LT with 50 (91%) first detected only by CT (P less than .001). These data reveal that CT detects more pulmonary metastases earlier than LT and that developing or growing nodules in patients with sarcomas are usually metastases. Decisions regarding metastasis resection in sarcoma patients, therefore, should be based primarily on CT findings.

Adolescent↗
PubMed1985

Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer.

During a randomized trial of total parenteral nutrition (TPN) in patients with small cell lung cancer, we evaluated the short- and long-term effects of 4 weeks of TPN on nutritional assessment parameters. All 119 patients who were accrued to the study received the same chemotherapy and radiotherapy protocol which extended over a 1-year period: 57 patients received TPN; and 62 served as controls. At base line, patients with greater than 5% pretreatment weight loss had significantly lower levels of serum albumin, total iron-binding capacity, and creatinine/height index. TPN administration led to a significant increase in mean caloric intake and weight compared with controls (P less than 0.0001). In the short-term study, body fat, as measured by triceps skinfold thickness, was maintained, and there was a small increase in arm muscle circumference. Serum albumin and hematocrit decreased but promptly returned to pretreatment levels when TPN was stopped. There were no long-term differences in any of the nutritional assessment parameters between the two groups.

Adipose Tissue↗
PubMed1983

Delayed hypersensitivity skin testing as a prognostic indicator in patients with small cell lung cancer.

The prognostic importance of pretreatment delayed hypersensitivity skin test reactivity was determined in 154 newly diagnosed, carefully staged and aggressively treated small cell lung cancer patients. One hundred twenty-one patients were reactive to at least 1 of 5 skin test antigens and 33 were anergic. Skin test reactive patients survived significantly longer than anergic patients. This result was expected since there was a significant trend for reactive patients to have good performance status (P = 0.005) and low tumor burden (P = 0.005) compared to anergic patients. The principal finding of this study was that skin test reactivity was of prognostic utility primarily in otherwise good prognosis patients, i.e., individuals with good performance status and low tumor burden. In this group anergy was associated with significantly shortened survival (P = 0.025). In poor prognosis (poor performance status and high tumor burden) or intermediate prognosis (either poor performance status or high tumor burden) patients skin test reactivity or anergy had no significant influence on survival.

Adult↗
PubMed1983

Intensive combined modality therapy including low-dose TBI in high-risk Ewing's Sarcoma Patients.

Twenty-four high-risk Ewing's sarcoma patients were treatedf on an intensive combined modality protocol including low-dose fractionated total body irradiation (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patients with a single metastasis were again rendered disease-free and remain free from second relapse with 18 and 30 months follow-up. No other relapsed patient was able to be rendered disease-free, and most died of progressive disease within 6 to 12 months of relapse. Two patterns of granulocyte recovery following consolidative therapy (include TBI) and ABMI were recognized. Seventeen patients reached a total granulocyte count of >500 cells/mm3 within 4 weeks of ABMI (early graulocyte recovery), while seven patients required >4 weeks from ABMI (late granulocyte recovery). The time of platelet recovery (>50,000/mm3) was different for the groups with early and late granulocyte recovery (25 days vs. 54 days, p <.001). Six of seven patients with late granulocyte recovery received locl high-dose irratiation to >1/2 pelvis prior to bone marrow storage. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when compaing the groups with early and late granulocyte recovery. We conclude that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy include low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

Adolescent↗
PubMed1982

Experience of the National Cancer Institute (USA) in the treatment and biology of small cell lung cancer.

This retrospective study deals with 168 patients with small cell lung cancer (SCLC) who were treated at the NCI March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 per cent of all the patients were disease-free for more than 40 months (25% of the limited disease and 3% of the extended stage disease patients which were treated. Complete remission was essential to prolonged survival. The development of a complete remission was favored by a satisfactory initial general condition, localised disease or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may induce a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This lead the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal cord block above 2 000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are not underway using intensive chemotherapy with multiple tumor site irradiation and autologous marrow implants 48 per cent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease whereas only 40 per cent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. Inspite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI. - Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of APUD system and are secreted by the SCLC. Bombesine has been isolated in all the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. - These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. - In vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). - Lastly, monoclonal AC have been prepared. Inspite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

Antineoplastic Agents↗
PubMed1981

Growth of lung cancer colonies from bronchoscopy washings.

Cells from bronchoscopy washings from 30 patients with lung cancer were plated in tissue culture using a human tumor stem cell assay technique. These culture results were subsequently compared to routine cytology readings carried out on the same specimens. The stem cell culture showed colony growth from 9 of 11 cytologically positive bronchoscopy washing specimens. More colonies grew from cytologically positive specimens (average of six colonies per plate) than from cytologically negative specimens (average of 0.8 colonies per plate). With additional refinements, the stem cell culture system could be used to improve the diagnostic yield of bronchoscopy washings. However, at present, the low number of tumor colonies grown from the washings precludes performing chemosensitivity studies on tumor cells from the bronchoscopy washing specimens.

Bronchoscopy↗
PubMed1981

Peritoneoscopy in the management of ovarian cancer.

The results obtained from the routine use of peritoneoscopy in the initial evaluation and follow-up of 99 patients with ovarian cancer treated at the National Cancer Institute between 1970 and 1978 have been analyzed. Prior to treatment, peritoneoscopy documented new sites of involvement undetected by conventional radiologic and isotopic procedures in 42 patients (48%) and provided the only evidence for follow-up of disease in 25 patients (28%). Twenty-one percent of patients referred with Stages I and II disease were upstaged to Stage III on the basis of diaphragmatic disease detected at peritoneoscopy. In the 66 restaging (posttreatment) peritoneoscopies, residual disease was found in 33 (50%) and peritoneoscopic findings provided the only evidence for disease in 24 cases (36%). These patients were spared an unnecessary second-look laparotomy. Twenty-two patients with negative peritoneoscopies underwent laparotomy. Residual ovarian cancer was found in 12 (55%), mainly in the pelvis and mesentery. Thus, a negative peritoneoscopy must be followed by a laparotomy before a patient with ovarian cancer can be considered disease free. Peritoneoscopy was found to be a safe and feasible procedure, even in patients who had prior laparotomies. It could not be performed for technical reasons in only 6% of the patients. There were few serious complications and in only 2.5% of the cases was medical therapy required to deal with a complication. There were no deaths or perforations of the viscus and no patient required surgical exploration because of a peritoneoscopy complication.

Abdominal Neoplasms↗
PubMed1981

Association between human tumor colony-forming assay results and response of an individual patient's tumor to chemotherapy.

An in vitro tumor colony-forming assay was utilized to measure the sensitivity of 800 individual patients' tumors to a variety of antineoplastic agents. Thirty-six separate histologic types of cancer were represented. Only 199 of the 800 patients' tumors (25 percent) both formed colonies in vitro and had enough cells in the biopsy or fluid specimen to perform drug sensitivity assays. In 123 instances the drug tested in vitro against the tumor was also used clinically to treat the patient. The clinician caring for the patient did not know the results of the in vitro test. When analyzed in a retrospective manner, the probability of a positive prediction from the assay, given the patient responded clinically, was 0.88. The probability for a negative prediction of the assay given the patient did not respond, was 0.94. Associations of in vitro and in vivo results in the 123 correlations were highly significant (p less than 0.001). We conclude that, as now constituted, the human tumor colony-forming assay can provide useful sensitivity information for only about 25 percent of the general oncology patients. Secondly, a prospective clinical trial of the assay is needed to insure that the assay is indeed predictive of which drug will produce a patient response and that it is not merely an indicator that a particular patient's tumor is highly responsive in vivo.

Antineoplastic Agents↗
PubMed1980

Smoking abstinence and small cell lung cancer survival. An association.

The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival.

Carcinoma, Small Cell↗
PubMed1980

Determination of prognostic factors and their influence on therapeutic results in patients with Ewing's sarcoma.

We have analyzed the results of treatment of 117 patients with Ewing's sarcoma admitted to the National Cancer Institute since 1964. All patients received local irradiation to the primary site and a series of progressively more intensive systemic chemotherapy regimens using drugs known to be active as single agents in this disease. Four protocols were employed with varying numbers of patients in each treatment group. Initially, there appeared to be a difference among treatment groups with regard to disease-free survival (overall P = .06), with the later regimens having more favorable outcomes. We then undertook a statistical analysis of the influence of five pretreatment variables--age, sex, site of primary disease, serum lactic acid dehydrogenase (LDH), and metastatic status--on disease-free survival. Of these five factors, important indicators of favorable prognosis for the entire group (and for each of the treatment subgroups) were a distal site of primary disease, normal serum lactic acid dehydrogenase (LDH) level at presentation, and the absence of metastatic disease at the time of presentation. When we examined treatment results with respect to these prognostic factors, we found that the subgroups treated with the more agressive regimens contained higher proportions of patients with favorable prognostic factors. After adjustment for differences in composition of treatment groups with respect to prognostic factors, the apparent difference in disease-free survival vanished (P = .62). These results indicate that in the case of Ewing's sarcoma, prognostic factors must be carefully considered in the design of treatment protocols and the subsequent analysis of end results.

Age Factors↗
PubMed1980

Direct cloning of human neuroblastoma cells in soft agar culture.

An in vitro soft agar technique was used in an attempt to culture neuroblastoma cells from 71 bone marrow, 3 lymph node, and 2 solid tumor specimens from 18 patients with neuroblastoma. One-half of each specimen was sent for routine pathology studies and one-half was cultured in the soft agar system. Colonies appeared within 10 days in histologically positive bone marrows. Light microscopy, electron microscopy, catecholamine secretion, and karyology provided evidence that the colonies were composed of neuroblastoma cells. There were 38 instances in which histological study of the specimen demonstrated neuroblastoma cells. The soft agar system showed colony growth in 30 of these samples (79%). There were a total of 38 specimens that were histologically negative for neuroblastoma. Thirty of these 38 specimens showed no growth in the stem cell assay. Eight histologically negative specimens from 6 patients formed colonies in the soft agar system. Five of these 6 patients showed tumor histologically on prior or subsequent marrow examinations. In addition to a significant correlation between histological and soft agar culture results (p < 0.001), there exists a highly significant positive correlation between the number of colonies per plate and the histological status of the specimen (p < 0.005). Serial marrow samples were cultured on 7 patients. There appears to be an association between the number of colonies that develop in the plate and the clinical course and prognosis of the patient. Decreasing plating efficiencies (number of colonies per number of cells plated) correlated with tumor response. Increasing plating efficiencies indicated tumor relapse. A plating efficiency of greater than or equal to 0.1% portended a particularly poor prognosis. Neuroblastoma grows well in this soft agar culture system. This excellent growth provides a good model for both clinical and basic science studies of neuroblastoma.

Abdominal Neoplasms↗
PubMed1980

The role of bone scans in assessing malignant melanoma in patients with stage III disease.

Two hundred abnormal bone scans of patients with a malignant melanoma were reread in a blinded fashion to identify osseous metastases. These findings were compared with serum calcium and alkaline phosphatase levels, skeletal surveys and survival curves of the same patients. Thirty-four of the 38 patients classified as positive for osseous metastases by bone scans ultimately supported that diagnosis. Three patients have probable, but not proved, osseous metastases, and one patient is classified as false-positive. Identification of osseous metastases by skeletal surveys never preceded bone scan identification. Skeletal surveys were most helpful in the identification of a benign condition which caused scan positivity. Serum calcium and alkaline phosphatase levels were never as sensitive or specific as either scans or surveys. In two patients with progressive osseous disease, the levels fell. We believe that radionuclide bone scans should be the first diagnostic procedure for suspected osseous metastases in patients with a malignant melanoma. It appears to be a more sensitive and specific test than skeletal surveys or serum calcium and alkaline phosphatase levels. We believe its use as a first test would save time, money and needless surgical procedures.

Adult↗
PubMed1979

Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Antineoplastic Agents↗
PubMed1979

Recommendations for the analysis of the effect of treatment on the development of second malignancies.

Use of the person-years method for evaluating the association between treatment of a primary cancer and subsequent development of a second malignancy is reviewed. For this type of analysis, the risk of developing a second malignancy is implicitly assumed to remain constant during each patient's follow-up period; this assumption is shown to be inappropriate. When the oncogenic potential of two or more treatments is compared, results are biased unfavorably against the use of intensive treatments that prolong life. Misinterpretation of the oncogenic potential of such treatment regimens can therefore occur, and two alternative statistical techniques are proposed, each for use in a commonly encountered experimental situation. These fairly classic methods of survival analysis are recommended to ascertain the relationship between treatment and development of a second cancer.

Antineoplastic Agents↗