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Biomedical subjects

F R Hirsch

Publications and source records attributed to F R Hirsch.

At least 55 records · Page 3Linked to original sources
PubMed1992

The impact of abdominal computerized tomography on the pretreatment staging and prognosis of small cell lung cancer.

One hundred six patients with small cell lung cancer (SCLC) were prospectively evaluated with regard to the prognostic impact of abdominal CT-scan in the pretreatment staging when compared to ultrasonography of the abdomen. Staging based on abdominal ultrasonography (US) plus bilateral bone marrow examinations gave as a result that 47 patients had extensive disease (ED) (44%). Seventeen patients with proven ED at time of referral were not included in this study. Abdominal CT-scan was performed in 76 of the 106 patients. Thirty patients of these 76 patients (39%) were classified as having ED after staging including US, but abdominal metastases were disclosed in another ten patients at the subsequent CT-scan. Liver metastases seen in two patients at ultrasonography were overlooked on the CT-scans. Median survival of the 36 patients classified as having limited disease (LD) after both procedures was 458 days, which was significantly better compared to 330 days for the ten patients with stage migration from LD to ED based on CT-scan, (p less than 0.05) and compared to 242 days in the 30 patients with ED demonstrated by both US and CT-scans (p less than 0.05). The prognostic impact of the CT-scan was further investigated in a multivariate analysis (Cox). Stage disease, performance status, LDH and alkaline phosphatase were significant prognostic factors in a proportional hazards model based on the original 106 patients. Patients in the best prognostic group were characterized by LD, good performance status (0-1) and normal LDH and alkaline phosphatase serum values. This group consisted of 22 patients (21%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1991

Occurrence of neuron specific enolase in tumour tissue and serum in small cell lung cancer.

An analysis has been made of the relationship between neuron specific enolase (NSE) in serum and immunohistochemically identified occurrence of NSE in the primary tumour in 56 patients with small cell lung cancer (SCLC). Patients were referred to the Finsen Institute for treatment during a period of 18 months. Forty-six tumours (82%) were NSE positive. To compare this staining with the occurrence of NSE in serum, a histological staining index (HSI) was established by semiquantitative gradation of the staining. No significant differences were found between distribution of serum NSE values in different HSI categories, and a high ranking in HSI was not associated with a high level of serum NSE. Both univariate and multivariate analysis selected serum NSE and not HSI as the most influential prognostic factor in SCLC.

Animals↗
PubMed1991

Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens.

The outcome of two different alternating regimens of chemotherapy was investigated in a prospective controlled trial in limited-stage small-cell lung cancer (SCLC). Both regimens comprised cyclophosphamide, lomustine, vincristine, methotrexate, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneous administration of cyclophosphamide + lomustine alternating with cyclophosphamide + doxorubicin, and with doxorubicin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentiated efficacy of the three specific combinations. A total of 234 patients were included, and 113 vs 108 patients were eligible. Median survival in both groups was 48 weeks (p = 0.89). Complete remissions were observed in 36/101 and in 42/99 patients evaluable for response. There was no significant difference in response duration. At restaging after 18 months of chemotherapy 27 patients (16%) and 22 patients (16%), respectively, were free of disease. Six patients, three in each arm, are still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless, regimen B resulted in significantly more leukopenic patients, septicemic episodes, and blood transfusions, and the dosage of etoposide was more often reduced in arm B than in arm A. The increased toxicity was not associated with improved treatment results.

Adult↗
PubMed1991

Prognostic impact of histologic demonstration of chromogranin A and neuron specific enolase in pulmonary adenocarcinoma.

One hundred-fourteen patients with inoperable adenocarcinoma of the lung (ACL) were evaluated by immunohistochemistry with monoclonal antibodies against Neuron Specific Enolase (NSE) and Chromogranin A (Chr A) in order to determine the frequency and prognostic impact of such antigen expression. All patients were previously untreated and received chemotherapy according to a prospective randomized trial. The tumors of 18 patients (16%) had more than 10% positive cells stained with anti-NSE, 59 (52%) had 1-10% positive cells and those of 37 patients (32%) contained no NSE-positive cells. The corresponding figures for Chr A were: 22 patients (19%), 51 patients (45%) and 41 patients (36%), respectively. Forty-four per cent of the patients with more than 10% positive NSE cells responded to chemotherapy (either complete or partial remissions) compared to 17% of the patients with fewer than 10% positive cells (p less than 0.025). The corresponding values for Chr A were 30% responders versus 19% responders (not statistically significant). The median survival for patients with more than 10%, 1-10% or no NSE-positive cells was 262 days, 231 days and 159 days, while, for Chr A it was 245 days, 200 days and 238 days, respectively. The survival curves for both NSE and Chr A according to the various levels of positivity were not significantly different. The presence of neuroendocrine marker in pulmonary adenocarcinoma seems to be associated with increased sensitivity to chemotherapy.

Adenocarcinoma↗
PubMed1991

Expression of 'small cell carcinoma antigens' in primary small cell lung cancer and metastases: an immunohistochemical study.

The presence of 'small cell lung cancer antigens' was evaluated in pretreatment biopsies of primary SCLC, liver metastases, and/or bone marrow metastases from 46 patients. The antigen expression was detected immunohistochemically by applying monoclonal antibodies to routinely formalin-fixed and paraffin embedded tissue. The antibodies applied were second workshop codes: 3(CAM 5.2), 45 (MOV15), 54 (NCCST433), 75 (PE35), 81 (HMFG-1), 95 (LCA1/L38) and HMFG-2 123C3, F4 and MOC-21. High expression was observed for WS 3, 45, 75, 81 and HMFG-2, both in the primaries and metastases. A good correlation was observed between the presence of antigens in primary biopsies and metastases, but there was a general tendency toward a lower proportion of positive tumour cells in the metastases compared to the primaries. For WS 45, 54, 75 and 95 the difference between primaries and bone marrow was statistically significant, and this was also true for WS 45 and 81 in the liver. The clinical relevance is discussed.

Antibodies, Monoclonal↗
PubMed1988

Histopathologic classification of small cell lung cancer. Changing concepts and terminology.

Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

Carcinoma, Small Cell↗
PubMed1988

The prognostic implication of histopathologic subtyping of pulmonary adenocarcinoma according to the classification of the World Health Organization. An analysis of 259 consecutive patients with advanced disease.

The prognostic impact of subtyping pretreatment histologic material in adenocarcinoma of the lung (ACL) according to WHO was evaluated in 259 consecutive, inoperable, Stage III patients. One hundred thirty patients (50%) had acinar adenocarcinoma, 23 (9%) had papillary adenocarcinoma, 13 (5%) had bronchioloalveolar carcinoma, and 32 (12%) had solid carcinoma with mucus formation; five patients (2%) had other types of lung cancer. Subtyping was impossible due to cytology or insufficient histologic material in 56 patients (22%). Bronchioloalveolar carcinoma had the longest median duration of response to chemotherapy (47 weeks), time to progression (33 weeks), and median survival (40 weeks). Corresponding values for solid carcinoma with mucus formation were 8, 12, and 22 weeks. Acinar and papillary adenocarcinoma were intermediate. Survival curves and response rates were similar (P greater than 0.05). Bronchioloalveolar carcinoma had 46% 1-year survivors compared to 16% to 22% for other subtypes. The subtypes may have an impact on the prognosis of ACL, but further evaluation is required.

Adenocarcinoma↗
PubMed1987

Metastatic patterns in small-cell lung cancer: correlation of autopsy findings with clinical parameters in 537 patients.

Postmortem material from 537 patients included in various protocols of intensive combination chemotherapy or chemoradiotherapy for the management of small-cell anaplastic carcinoma of the lung (SCLC) has been reviewed. Patterns of residual or recurrent disease were analyzed in relation to pretreatment clinical parameters. Residual primary tumor (P less than .05), regional lymph node involvement (P less than .01), hepatic (P less than .01), bone (P less than .05), and renal metastases (P less than .05) were all significantly less frequent among patients with initially limited-stage disease compared with extensively staged patients. The frequency of residual intrathoracic tumor and metastatic pattern did not significantly differ between partial responders (PRs) and nonresponders (NRs). Patients with limited disease achieving a complete remission had a lower frequency of intrathoracic tumor (P less than .001) at autopsy compared with limited-stage PRs. However, for extensive-stage patients the pattern of residual disease was essentially independent of tumor response. Prior surgery was associated with a reduced burden of metastases only in those who underwent a radical resection. The addition of radiotherapy to the primary tumor and mediastinum failed to modify the autopsy distribution of residual tumor compared with that in patients treated with chemotherapy alone. Metastatic patterns were similar with or without prophylactic abdominal radiotherapy, while prophylactic cranial irradiation (PCl) did not prevent the development of cerebral metastases in patients whose systemic response to treatment was either partial or nonexistent. However, a beneficial effect of PCl in compete responders (CRs) was not excluded.

Carcinoma, Small Cell↗
PubMed1987

The superiority of combination chemotherapy including etoposide based on in vivo cell cycle analysis in the treatment of extensive small-cell lung cancer: a randomized trial of 288 consecutive patients.

Two hundred and eighty-eight patients with extensive small-cell carcinoma of the lung (SCCL) were entered into a three-arm prospective randomized trial. The purpose was both to compare etoposide with methotrexate (MTX) in a combination chemotherapy regimen otherwise consisting of vincristine (VCR), lomustine (CCNU), and cyclophosphamide (CTX) and to evaluate a treatment design based on cell kinetic observations suggesting enhanced sensitivity to etoposide three to six days after administration of VCR, CCNU, and CTX. In all three treatment arms, VCR, CCNU, and CTX were administered on day 1 of a 28-day cycle. In arm A, MTX was administered on days 14 and 17, while in arm B, MTX was replaced by etoposide administered on days 14 through 17. In arm C, MTX was also replaced by etoposide, but administered on days 3 through 6. Overall survival was significantly longer for patients treated with "early" etoposide (arm C; median, 33 weeks) as compared with arm A (MTX; median, 23 weeks) (P less than .05), but not statistically different from "late" etoposide administration (arm B; median, 27 weeks). However, for patients with initial favorable performance status (0 + 1), a significantly longer survival was obtained for those treated with early etoposide (arm C. median, 51 weeks) as compared with patients in arm A (median, 32 weeks) and arm B (median, 36 weeks) (P less than .05). Two-year survival was obtained in six patients (7%) in arm C compared with three patients (3%) in arm B and none in arm A. The study confirmed that etoposide is an active drug in the treatment of SCCL and when combined with CTX, CCNU, and VCR, the cell kinetic approach of an early administration yields the best results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Morphologic variations of small cell lung cancer. A histopathologic study of pretreatment and posttreatment specimens in 104 patients.

A consecutive series of 104 autopsies on patients treated in protocol for small cell carcinoma of the lung (SCCL) was studied with respect to metastatic pattern at autopsy in relation to pretreatment WHO 1981 classification, and extent and significance of non-SCCL tumor tissue at autopsy. The only significant difference in the metastatic pattern at autopsy between patients with pretreatment oat cell or intermediate subtype was metastases to the brain. Thus, the frequency of brain metastases was 17/35 (49%) in patients with oat cell type compared to 2/18 (11%) in patients with intermediate type (P less than 0.05). At autopsy 13 of 98 patients (13%) had non-SCCL tumor tissue in at least one site. These patients had a significantly shorter survival (P = 0.020) compared to patients with pure SCCL at autopsy. Furthermore, none of these 13 patients had obtained complete remission. Whether these morphologic variations had been present at the pretreatment stage of the disease or were due to the chemotherapeutic treatment could not be solved in the present study. However, the results might indicate that mixed SCCL/non-SCCL histology is a negative prognostic factor in the treatment of SCCL. Prospective studies including more extensive pretreatment tissue sampling seem to be required.

Adult↗
PubMed1983

The prognostic significance of histopathologic subtyping of small cell carcinoma of the lung according to the classification of the World Health Organization. A study of 375 consecutive patients.

Three hundred seventy-five consecutive patients treated with intensive chemotherapy in the same institution are included in this study in order to evaluate the prognostic significance of the World Health Organization's (WHO) subclassification of small cell lung cancer. Morphologic subtyping, based on primary biopsy specimens, was obtained in 200 patients. Oat cell type was diagnosed in 106 patients (53%), while intermediate subtype was diagnosed in 93 patients (47%), including 27 patients (14%) with small cell/large cell morphologic features. One patient had combined oat cell type. No difference in survival period was observed between the group of patients classified as oat cell versus the group with intermediate subtype. However, a significantly shorter survival period was demonstrated for patients with small cell/large cell features compared with patients with pure small cell carcinoma (median 168 days versus 280 days, P less than 0.01). It is concluded that there is no difference in survival period between patients with oat cell and intermediate subtype of small cell lung cancer using the criteria of the WHO. However, it might be of prognostic importance to identify patients with tumors demonstrating small cell/large cell features.

Adult↗
PubMed1983

Intracranial metastases in small cell carcinoma of the lung. Prognostic aspects.

Two hundred-twelve consecutive patients with small cell carcinoma of the lung were studied in order to correlate the risk of developing intracranial metastases to the initial stage of the disease (locoregional versus extensive) and to evaluate the prognostic significance of developing intracranial dissemination of the disease. Clinically detected intracranial metastases were observed in four percent at the time of primary diagnosis, and an additional 18 percent developed metastases during treatment. As regards clinically observed metastases during treatment, no difference was found between the two initial staging groups. Intracranial metastases without clinical evidence of progressive disease elsewhere were demonstrated in 10 out of 205 patients (5%). The median survival time after clinical presentation of intracranial metastases was 85 days for patients with locoregional disease versus 60 days for patients with extensive disease. A significantly shorter survival time was observed for patients with intracranial metastases at 0, 100, 200 and 300 days after start of treatment compared to patients still alive without metastases at those times. Brain autopsy was performed in 82 patients and was positive in 42 (51%). No statistical difference in the frequency of brain metastases was demonstrated when compared to the initial stage of the disease. No difference was observed between the two initial staging groups of patients with regard to risk of developing brain metastases. Autopsy substantiated that there was no difference between patients with and without brain metastases as regards survival. However, clinical intracranial metastases were followed by a short survival time, and only a small fraction of the patients developed clinically isolated intracranial relapse.

Aged↗
PubMed1983

Tumor heterogeneity in lung cancer based on light microscopic features. A retrospective study of a consecutive series of 200 patients, treated surgically.

In order to study the problem of morphological tumor heterogeneity in lung cancer, 200 consecutive patients who had undergone surgery for a malignant lung tumor, were evaluated retrospectively with regard to morphological type. The tumor was classified morphologically in 187 patients, and 163 (87%) had a morphologically homogeneous tumor, based on light microscopic features and using the criteria recommended by the World Health Organization. The remaining 24 patients (13%) had a tumor with morphologic features of more than one cell type. It is concluded that morphological heterogeneity is a considerable problem in the classification of malignant lung tumors. This heterogeneity had been regarded as evidence of an endodermal origin of all major types of lung cancer. Future prospective studies will have to determine whether it has any therapeutic significance.

Adenocarcinoma↗
PubMed1983

Electron microscopic sub-classification of small cell carcinoma of the lung.

An electron microscopic study of 28 small cell carcinomas of the lung is presented. Cytoplasmic secretory granules, characteristic of endocrine cells of the human foetal lung were observed in a variable number of tumor cells. Two groups of tumors could be distinguished based on the morphology of the cytoplasmic secretory granules. Twenty-three tumors showed cells with granules resembling type 1 or P1 cells of the human fetal lung, and 5 tumors with granules resembling type 3 cells of the human fetal lung. No relationship was found between the light microscopic WHO classification of small cell carcinoma of the lung and the results obtained by electron microscopy. Increased serum calcitonin as well as inappropriate ADH secretion may be correlated with one of the two types of small cell carcinoma, but further investigations are needed.

Adrenocorticotropic Hormone↗