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R Gelman

Publications and source records attributed to R Gelman.

At least 91 records · Page 5Linked to original sources
PubMed1989

Can the clinical and mammographic findings at presentation predict the presence of an extensive intraductal component in early stage breast cancer?

The presence or absence of an extensive intraductal component (EIC) in early stage infiltrating ductal breast carcinoma has been considered to be an important factor in determining the extent of breast resection required prior to radiation therapy. It would therefore be useful if the presence or absence of an extensive intraductal component in a breast tumor could be predicted pre-operatively. To determine whether selected radiographic features might be correlated with whether or not a cancer is EIC+, we reviewed the pre-operative mammographic findings in 105 cases of Stage I and II infiltrating ductal carcinoma. Forty-one cases were EIC+ and 64 were EIC-. Both EIC+ and EIC- tumors were commonly detectable by mammography (93% and 83%, respectively, p = NS). EIC+ cancers, however, were significantly more likely to show microcalcifications with or without a mass compared to EIC- cases (83% vs 27%, p less than 0.0001). In particular, the presence of microcalcifications without a mammographic mass was more common for EIC+ cancers than EIC- cancers (34% vs 5% p = 0.0002). Conversely, a soft tissue mass without microcalcifications was seen mammographically in 56% of EIC- cases, compared to only 10% of EIC+ cases (p less than 0.0001). Predictive value calculations showed that the presence of microcalcifications in the absence of a mammographic mass conveys a 73% likelihood a cancer will be EIC+ (95% confidence interval = 39-94%). The positive predictive value of a mammographic mass or architectural distortion without microcalcifications for an EIC- cancer was 92% (95% confidence interval = 79-98%). We conclude that the mammographic findings may be useful pre-operatively in differentiating between patients with and without an EIC. Microcalcifications are much more commonly associated with EIC+ cancers than EIC- cancers, and the presence of an EIC- cancer without a mammographic mass is infrequent. Further characterization of the extent and pattern of microcalcifications might improve the predictive value of mammography in the pre-operative identification of patients with an EIC.

Adult↗
PubMed1989

Can sonographers reliably identify anatomic features associated with Down syndrome in fetuses?

To standardize femur measurement for the identification of fetuses at risk for Down syndrome, sonographers of varying professional experience and background measured the femurs of 20 Down syndrome fetuses and 709 normal control fetuses. A regression analysis performed to compare biparietal diameter to femur length on the 709 control fetuses yielded the following formula: expected femur length = -9.3105 + 0.9028.biparietal diameter. A ratio of measured-to-expected femur length of 0.91 or lower indicated Down syndrome with a sensitivity of 40%, a specificity of 95%, and a positive predictive value of 3.1%. Eight of the 20 fetuses with Down syndrome (40%) also had a thickened nuchal fold (6 mm or larger). If the nuchal fold findings had been considered with the femur length findings, two more of the fetuses with Down syndrome would have been identified, yielding a sensitivity of 45% and a positive predictive value of 4.3%. Because these measurements were made by eight sonographers rather than a single experienced sonologist, these results could be achieved in most ultrasound laboratories where measurements are done primarily by sonographers.

Down Syndrome↗
PubMed1988

Comparison of CA15-3 and carcinoembryonic antigen in monitoring the clinical course of patients with metastatic breast cancer.

Fifty-three women with metastatic breast cancer and serial plasma samples were selected to study the correlation between disease course and variations in circulating CA15-3 and carcinoembryonic antigen (CEA) levels. Forty-nine patients had their first sample drawn at the beginning of therapy, while four patients did not receive any treatment during the period of study. Clinical course was scored as progressive disease (PD), responsive disease (RD), and stable disease on the basis of radiological and physical evaluations. The percentage of variation in antigen level between the initial sample and samples drawn at the time of the clinical evaluation was correlated with clinical course. CA15-3 levels above 22.0 units/ml and CEA levels above 3.0 ng/ml were considered elevated values. Antigen levels that increased greater than or equal to 25% and decreased greater than or equal to 25% from the initial value were considered to correlate with PD and RD, respectively. Variations in antigen levels +/- 25% from the initial value were considered to correlate with stable disease. Significantly more patients had elevated circulating levels of CA15-3 than CEA (96.2 versus 69.8%; P less than 0.01) at some point in the course of disease. Overall, CA15-3 correlated with disease progression, regression, or stability in a higher number of patients than CEA (60.3 versus 39.6%; P = 0.02). CA15-3 increased greater than or equal to 25% more often than CEA in patients with PD (75.0 versus 58.3%) and decreased greater than or equal to 25% more often than CEA in patients with RD (38.1 versus 23.8%). In a logistic regression model, changes in CA15-3 levels correlated significantly with both PD (P = 0.0004) and RD (P = 0.02), while changes in CEA levels did not (PD, P = 0.34; RD, P = 0.92). Furthermore, correlations obtained when using both antigens together failed to improve the results obtained with CA15-3 alone. The present study thus demonstrates that CA15-3 is more useful than CEA in monitoring the clinical course of patients with metastatic breast cancer.

Algorithms↗
PubMed1988

Sonographically estimated fetal weights: accuracy and limitation.

To determine the accuracy of our ultrasonographically predicted birth weights we studied 1301 women delivered of infants within a week of an obstetric ultrasonogram to compare the ultrasonographically predicted birth weights with the actual birth weights. The fetuses varied from 700 to 5800 gm and were consecutive singleton fetuses in vertex presentations delivered at a single institution. Overall 74% of the infants had birth weights within 10% of the ultrasonographic estimates and 42% had birth weights within 5% of the ultrasonographic estimates. The presence of oligohydramnios or polyhydramnios made no difference in the percent errors. The sensitivity for identifying a fetus with macrosomia (birth weight greater than 4000 gm) with an estimated weight of greater than or equal to 4000 gm was 65%. The specificity or percent of fetuses correctly identified ultrasonographically as not macrosomic was 90%. If fetuses predicted by ultrasonography to be greater than 3800 gm were included, the sensitivity for the prediction of macrosomia rises to 82% but the specificity would be 79%. There appears to be a fixed limitation to obtaining estimated fetal weights by ultrasonography, even in large series, because these data reaffirm the success and limitations of other methods used to estimate fetal weight previously reported in the literature.

Birth Weight↗
PubMed1988

Murine chromosomal regions correlated with longevity.

In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room. Each strain had been typed for markers of 141 regions on 15 chromosomes; 101 of these markers had distinguishable distributions on the 20 strains. The two shortest lived strains had the same alleles for 63% of the markers. The single region most significantly correlated with survival (marked by P450, Coh, Xmmv-35 on chromosome 7) divided the mice into two groups with survival medians which differed by 153 days (755 days for mice with a B genotype; 602 days for mice with a D genotype). Evaluated individually, 44% of the genetic markers (including some markers on 11 of 15 chromosomes with any markers typed) were found to be significantly correlated with survival (P less than 0.05) although one would only expect 5% of the markers to be significant by chance. While studies of many markers should adjust for the multiple comparisons problem, one interpretation of these crude P values is that any experiment with only one of these "significant" markers typed would be likely to conclude that the marker was a significant predictor of survival. Two types of multiple regression models were used to examine the correlation with survival of groups of genes. When a proportional hazards model for survival was done in terms of genotype regions, a six genetic region model best correlated with survival: that marked by P450, Coh, Xmmv-35 on chromosome 7 (B allele lives longer), Ly-24 on chromosome 2 (B allele lives longer), beta 2M and H-3 on chromosome 2 (D allele lives longer) Lamb-2 on chromosome 1 (D allele lives longer), Ltw-4 on chromosome 1 (B allele lives longer), and the Igh area of chromosome 12 (Igh-Sa4, Igh-Sa2, Igh-Bgl, Igh-Nbp, Igh-Npid, Igh-Gte, Odc-8, and Ox-1; D allele lives longer).(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗
PubMed1988

Dose-response in the treatment of breast cancer: a critical review.

In animal tumor models the dose-response curve for cytotoxic agents, especially cyclophosphamide, may be steep, but the slope and shape of this curve depends not only on the drug used but on the schedule of drug administration, the specific tumor type, tumor cell kinetics, and tumor mass. It might be anticipated from these studies that the human tumors most sensitive to dose effects would be leukemia, lymphoma, small-cell carcinoma of the lung, and testicular tumors rather than the low growth fraction, relatively less responsive tumors such as breast cancer. However, the clinical evidence for a steep dose-response curve in any tumor type is limited. For breast cancer such evidence is largely retrospective or derived from uncontrolled trials. The data available from randomized trials makes it seem unlikely that small, or even moderate, reductions in drug dose for nontrivial reasons will compromise the survival of patients with either early or metastatic disease. In spite of promising data from small trials, there is, as yet, inadequate evidence to justify the use of very-high-dose therapy and autologous marrow transplant outside the setting of a well-designed clinical trial. The value of high-dose therapy, intensive dose rate, and cumulative drug dose should each be studied in randomized controlled trials.

Antineoplastic Agents↗
PubMed1987

Sonographic identification of second-trimester fetuses with Down's syndrome.

Fetuses with Down's syndrome are more likely than normal fetuses to have a thickened nuchal skin fold and relatively short femurs on ultrasound examination in the second trimester. We evaluated these measures in more than 5500 fetuses, including 28 who were later found to have Down's syndrome by means of amniocentesis with cytogenetic analysis. Normal femur length was established as a function of biparietal diameter in 192 of the normal fetuses. We found that with use of a nuchal skin-fold thickness of 6 mm or more and a ratio of actual to expected femur length of 0.91 or less, fetuses with Down's syndrome could be identified with a sensitivity of 75 percent and a specificity of 98 percent. When other anomalies, such as an atrioventricular canal and meconium peritonitis, were added to these two criteria, the sensitivity of sonographic detection of Down's syndrome in the second-trimester fetus rose to 82 percent. The potential predictive value of these sonographic signs far exceeds that of advanced maternal age and low alpha-fetoprotein levels, which currently identify only 10 to 30 percent of affected fetuses. We recommend that fetuses with a thickened nuchal skin fold or shortened femurs on ultrasound examination be evaluated for Down's syndrome by amniocentesis and cytogenetic analysis.

Amniocentesis↗
PubMed1987

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy.

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Young children's understanding of random phenomena.

2 experiments on the development of the understanding of random phenomena are reported. Of interest was whether children understand the characteristic uncertainty in the physical nature of random phenomena as well as the unpredictability of outcomes. Children were asked, for both a random and a determined phenomenon, whether they knew what its next outcome would be and why. In Experiment 1, 4-, 5-, and 7-year-olds correctly differentiated their responses to the question of outcome predictability; the 2 older groups also mentioned appropriate characteristics of the random mechanism in explaining why they did not know what its outcome would be. Although 3-year-olds did not differentiate the random and determined phenomena, neither did they treat both phenomena as predictable. This latter result is inconsistent with Piaget and Inhelder's characterization of an early stage of development. Experiment 2 was designed to control for the possibility that children in Experiment 1 learned how to respond on the basis of pretest experience with the 2 different phenomena. 5- and 7-year-olds performed at a comparable level to the same-aged children in Experiment 1. Results suggest an earlier understanding of random phenomena than previously has been reported and support results in the literature indicating an early understanding of causality.

Child↗
PubMed1986

Assessment of adjuvant trials in breast cancer.

In this paper, we discuss the analytic problems associated with the evaluation of overall survival for breast cancer adjuvant studies and results of pooling data from the published literature to determine if there is evidence showing an overall survival advantage to adjuvant therapy. An investigation of the effect of competing causes of death shows that trials on older patients have low statistical power. Hence many of the current trials have low statistical power and may fail to find overall survival advantage for adjuvant therapy even when a benefit exists. The implications of the assessment of short-term follow-up are discussed in the context of the heterogeneous distribution of residual disease after primary treatment. Short-term follow-up (less than 5 yr) precludes anyone from making any conclusions about benefit for patients with small residual tumor burdens who constitute the patient subgroup most likely to benefit from adjuvant therapy. We reviewed 15 published randomized trials (each having a control group receiving no systemic therapy) to determine if overall survival has been increased by adjuvant therapy. We conclude that there is a benefit from some chemotherapy regimens given to node-positive premenopausal women. However, the published data for tamoxifen are mixed, with some trials showing benefit and others not. As more follow-up time is accumulated, this matter should be settled.

Adult↗
PubMed1985

Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors.

One hundred fifty-five eligible women with metastatic breast cancer were randomly allocated to receive monthly cycles of either CMFP (cyclophosphamide, methotrexate, 5-fluorouracil, prednisone) or CAF (cyclophosphamide, doxorubicin, 5-fluorouracil), and 12 patients were studied to evaluate the effects of additional Corynebacterium parvum immunotherapy. Overall response rates of 53% were seen with CMFP and CAF. CAF was associated with significantly more complete responses than CMFP (17% v 5%). However, CAF therapy was administered for eight months and CMFP for six months. Only 13% of the CAF patients had a complete response during the first six months of chemotherapy, and this was not significantly different from the complete response rate on CMFP. The median response durations (CMFP, 6.3 months; CAF, 11.0 months), times to treatment failure (CMFP, 5.7 months; CAF, 7.8 months), and survival times (CMFP, 15.8 months; CAF, 18.6 months) were not statistically different. Other investigators who have compared CAF to CMF-containing regimens have reported a large advantage in CAF therapy among patients with "good risk" sites of metastases (local-regional recurrence, bone, lung nodules). Such a finding was not confirmed by our study: in multivariate analyses the groups associated with an advantage for CAF tended to have a poorer prognosis than the groups associated with an advantage for CMFP. There was significantly more nausea and vomiting after CAF treatment, and CMFP treatment was associated with significantly more edema, Cushingoid features, fever, and eye symptoms.

Adult↗
PubMed1985

Intracranial germ-cell tumors: natural history and pathogenesis.

The natural history of primary intracranial germ-cell tumors (GCT's) is defined from 389 previously published cases, of which 65% were germinomas, 18% teratomas, 5% embryonal carcinomas, 7% endodermal sinus tumors, and 5% choriocarcinomas. Intracranial GCT's display specificity in site of origin. Ninety-five percent arise along the midline from the suprasellar cistern (37%) to the pineal gland (48%), and an additional 6% involve both sites. The majority of germinomas (57%) arise in the suprasellar cistern, while most nongerminomatous GCT's (68%) preferentially involve the pineal gland (p less than 0.0001). The age distribution of afflicted patients is unimodal, centering with an abrupt surge in frequency in the early pubertal years; 68% of patients are diagnosed between 10 and 21 years of age. Nongerminomatous GCT's demonstrate an earlier age of onset than do germinomas (p less than 0.0001). Prolonged symptomatic intervals prior to diagnosis are common in germinomas (p = 0.0007), in suprasellar GCT's (p = 0.001), and among females (p = 0.02). Parasellar germinomas commonly present with diabetes insipidus, visual field defects, and hypothalamic-pituitary failure. Nongerminomatous GCT's present as posterior third ventricular masses with hydrocephalus and midbrain compression. Germ-cell tumors may infiltrate the hypothalamus (11%), or disseminate to involve the third ventricle (22%) and spinal cord (10%). Among a subpopulation of 263 conventionally treated patients, two factors were of prognostic significance: 1) histological diagnosis; germinomas were associated with significantly longer survival than nongerminomatous GCT's (p less than 0.0001); and 2) staging of the extent of disease; this emphasizes the ominous character of involvement of the hypothalamus (p = 0.0002), third ventricle (p = 0.02), or spinal cord (p = 0.01). Specific recommendations regarding the necessity of histological diagnosis and staging of the extent of disease are made in light of modern chemotherapeutic advances. The pathogenesis of GCT's may be revealed by their specificity of origin within the positive (suprasellar cistern-suprachiasmatic nucleus) and negative (pineal) regulatory centers for gonadotropin secretion within the diencephalon. The abrupt rise in age distribution at 10 to 12 years suggests that the neuroendocrine events of puberty are an "activating" influence in the malignant expression of these embryonal tumors.

Adolescent↗
PubMed1984

Utility of differential leukocyte counts in cancer management.

In 1,811 adult patients receiving diverse treatments for cancers other than leukemia, the absolute neutrophil count closely paralleled the total leukocyte (WBC) count. All of the 1,260 patients with WBC counts higher than 5,000/cu mm had more than 1,500 neutrophils per cubic millimeter. Routine differential leukocyte counts are rarely useful in managing the cancer therapy for patients with a WBC count greater than 5,000/cu mm, and only add to the cost of their care.

Adolescent↗
PubMed1983

Detection of intermodal numerical correspondences by human infants.

Infants prefer to look at an array of objects that corresponds in number to a sequence of sounds. In doing so, infants disregard the modality (visual or auditory) and type (object or event) of items presented. This finding indicates that infants possess a mechanism that enables them to obtain information about number.

Auditory Perception↗
PubMed1983

Management of locally advanced carcinoma of the breast by primary radiation therapy.

We performed a retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54%, 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced-breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

Adult↗