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Biomedical subjects

F R Hirsch

Publications and source records attributed to F R Hirsch.

68 records · Page 4Linked to original sources

Continuous versus alternating combination chemotherapy for advanced small cell carcinoma of the lung.

In a 2-year period, 146 patients with small cell carcinoma of the lung, staged as having extensive disease, were randomized to receive either continuous chemotherapy consisting of (a) 1-(2-chloroethyl-3-cyclohexyl-1-nitrosourea, cyclophosphamide, methotrexate, and vincristine followed by (b) 4'-demethylepipodophyllotoxin 9-[4,6-O-(R) ethylidene-beta-D-glucopyranoside] and doxorubicin at progression of disease or a regimen of (a) alternating with (b). Seventy-six patients received the continuous regimen; 70 patients received alternating treatment. Response rates were 68 and 72%, respectively. The median duration of response was 16 weeks in patients receiving continuous treatment compared to 28 weeks in patients receiving alternating treatment (p less than 0.05). No survival time difference was observed between the groups, median survival being 36 and 38 weeks, respectively. Four patients became long-term survivors (5.6 +, 5.5 +, 5.1, and 4.7 + years). All received alternating therapy. Six toxic deaths were observed among patients receiving continuous therapy compared to only one death among those in the alternating regimen. In conclusion, alternating combination chemotherapy leads to prolonged duration of remission. Duration of survival is not prolonged in uncured patients, but an increased possibility of long-term disease-free survival cannot be precluded.

Antineoplastic Combined Chemotherapy Protocols↗

Intracranial metastases in small cell carcinoma of the lung: correlation of clinical and autopsy findings.

Two hundred-twelve consecutive patients with small cell carcinoma of the lung were included in an evaluation of clinical and diagnostic neurologic findings of intracranial metastases. A correlation of premortem findings to postmortem examination of the brain was obtained in 87 of the patients. Clinical intracranial metastases were diagnosed in 21.2% on the basis of symptoms and signs. At autopsy 44 of the 87 patients (50%) had metastases. Lesions located to the posterior cranial fossa were demonstrated in 53% of the positive autopsies. A correlation of 96% existed between significant premortem clinical findings and positive autopsy, while 33% had clinically "silent" metastases at autopsy. A neuro-oncologic examination was performed in 49 patients at the time of presentation of neurologic symptoms. Twenty-eight patients were considered to have intracranial metastases. Gait disturbances were the presenting signs in more than 50% of the patients. Brain metastases were demonstrated at autopsy in 14 of 15 patients considered to have intracranial metastases by the neuro-oncologist, and clinically "silent" metastases were observed in one out of 10 patients. Radionuclide brain scan was negative in seven of 13 patients in spite of "positive" neuro-oncological examination had a subsequent positive autopsy. Cerebrospinal fluid examination was of no value in the diagnosis of brain metastases. It is concluded that a careful clinical examination by a neuro-oncologist is of great value in early detection of brain metastases, especially in diagnosing metastases to the posterior cranial fossa.

Autopsy↗

Histopathologic classification of small cell carcinoma of the lung: comments based on an interobserver examination.

In order to evaluate the consistency in diagnosing the morphologic subtypes of small cell carcinoma of the lung (SCCL), 93 microscopic slides were blindly classified by three panelists according to the World Health Organization's (WHO) Lung Tumor Classifications of 1967 and 1981. Unanimity in the diagnosis of SCCL as the main cell type was obtained in 91 and 94% respectively. With regard to the diagnosis of the various morphologic subtypes unanimity among the three panelists was achieved in 38% according to the WHO 1967 classification and in 54% using the 1981 classification. It is concluded that the criteria used for SCCL as a distinct histopathologic entity were reproducible among the different panelists. However, different criteria were applied in the diagnosis of the morphologic subtypes of SCCL. This fact could explain the contradictory results of clinical studies reported in the literature concerning subtyping of SCCL.

Autopsy↗

Histological examination for Z-gene alpha 1-antitrypsin deficiency in small cell anaplastic carcinoma of the lung.

Carriers of Z-gene alpha 1-antitrypsin deficiency (A-1-ATD) have characteristic periodic acid Schiff (PAS) positive diastase resistant globules in hepatocytes. In order to determine a possible relationship between Z-gene A-1-ATD and small cell carcinoma of the lung (SCCL), we examined liver blocks from 88 consecutive autopsies performed on patients with SCCL and from a control group of 88 patients with carcinoma not primarily located in the lung or the liver. Histological evidence of Z-gene-A-1-ATD was 4.5% in both groups, corresponding to the expected frequency of Z-gene carriers in a Scandinavian population. It is therefore unlikely that Z-gene A-1-ATD has a role in the development of SCCL.

Adult↗

Prophylactic irradiation in bronchogenic small cell anaplastic carcinoma. A comparative trial of localized versus extensive radiotherapy including prophylactic brain irradiation in patients receiving combination chemotherapy.

A total of 114 patients with bronchogenic small cell anaplastic carcinoma and staged as having regional disease all underwent combination chemotherapy consisting of CCNU, cyclophosphamide, and methotrexate. They were randomized to receive either radiotherapy to the primary tumor and regional lymph nodes (4000 rad) or extensive radiotherapy, which included the brain, adrenals, and upper retroperitoneal lymph nodes. Fifteen patients were free of disease after 18 months of chemotherapy and the treatment was discontinued. Only 3 patients subsequently relapsed. No difference was observed between the two groups of patients in median survival time, response rate, duration of response or relapse pattern, including the frequency of brain metastasis.

Adult↗

Bone marrow involvement in small cell anaplastic carcinoma of the lung: prognostic and therapeutic aspects.

One hundred ninety-three patients with untreated advanced small cell anaplastic carcinoma of the lung were divided into two groups on the basis of whether or not the pretreatment bone marrow examination revealed tumor. The groups were analyzed with regard to survival, treatment response, tolerated amount of chemotherapy, hematologic toxicity including necessity for blood transfusions, and episodes of clinical sepsis. The median survival time was significantly lower for patients with a positive bone marrow examination (149 days vs. 231 days) (P less than 0.01). Short survival times were especially observed for patients with bone marrow metastases and initial thrombocytopenia as compared to those with bone marrow metastases but normal platelet counts (68 days vs. 176 days) (P less than 0.05). The median duration of remission was 86 days for the groups with positive bone marrow examinations vs 182 days for the negative group (P less than 0.05). No difference was observed with regard to other parameters studied. It is concluded that a positive pretreatment bone marrow examination is an unfavorable prognostic indicator, especially for patients with additional thrombocytopenia, but it does not seem to be a restrictive factor for effective use of intensive chemotherapy in the treatment of small cell anaplastic carcinoma of the lung.

Antineoplastic Agents↗

Hormonal polypeptides and amine metabolites in small cell carcinoma of the lung, with special reference to stage and subtypes.

To elucidate the ectopic hormonal pattern in patients with small cell carcinoma of the lung, plasma ACTH, serum calcitonin, serum gastrin, plasma glucagon, serum insulin, plasma secretin, plasma VIP, serum growth hormone, serum hCG/LH, the total of serum hCG and hCG-beta-subunit,serum alpha-subunit, serum human placental lactogen, urine ADH, urine 5-HIAA, urine VMA, urine HVA, and urine hCG-LH were measured prior to therapy in 75 patients. Twenty-two patients (29%) had elevated plasma ACTH, and 18 of these had concomitant increased values of corticosteroid in a 24-hour urine sample. Forty-eight patients (64%) were found to have elevated serum calcitonin, and one-third of the patients were diagnosed as having the ectopic ADH syndrome. Serum gastrin concentrations were increased in 20% of the patients, but the elevations were marginal in almost all cases. None of the remaining substances was found to be significantly elevated. Concentrations of plasma ACTH, serum calcitonin, and urine ADH were not found to be correlated with the stage of the disease, and no correlation of these substances with the histological subtypes of small cell carcinoma was disclosed.

Adrenocorticotropic Hormone↗

Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis.

Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination and a newly developed procedure for storing aspirates at -80 degrees. Thirty-eight different metastases in 30 consecutive patients with small-cell anaplastic carcinoma of the lung were examined with a total of 273 fine-needle aspirations. The results on ploidy are reported in this paper. The degree of contamination of the aspirates with normal cells was determined by differential counts. The ratio of the peak channel numbers for the G1 phase of the tumor cells to that of the diploid standard (DNA index) was calculated and used for ploidy identification. Twenty-nine patients were evaluable with respect to DNA index determination. The coefficient of variation of the DNA index determinations was estimated as 0.039. In 23 (79%) patients, only one cell line could be detected. Evidence of the presence of 2 tumor cell clones with different ploidy was obtained in the remaining 6 (21%) patients. Of the 35 malignant clones thus demonstrated, 26 (74%) were significantly different from diploid (p less than or equal to 0.01). Four (11%) were hypodiploid, 3 (9%) were hypotriploid, and 19 (54%) were hypo- or near-tetraploid. Clonal heterogeneity in the tumors of 21% of the patients is a conservative estimate. Assessment of the detection limit set by the methodology used and the restricted number of samples studied in each patient indicate that the true occurrence of clonal heterogeneity in small-cell carcinoma of the lung may be much higher.

Aged↗

Bilateral bone-marrow examinations in small-cell anaplastic carcinoma of the lung.

Bilateral bone-marrow examinations from the posterior iliac crests were routinely performed as a pretreatment staging procedure in 89 consecutive patients with small-cell anaplastic carcinoma of the lung. Bone-marrow involvement was found in 20 patients (22.5%), in 9 (10.1%) only on one side, and in 11 (12.4%) on both sides. Aspiration was found to be significantly superior to biopsy, being positive in 25 examinations as compared with 14 positive biopsies. Compared with unilateral bone-marrow examination the positive findings increased by approximately 30%. Bilateral bone-marrow examinations are recommended in patients in whom the detection of bone-marrow metastases will have therapeutic implications.

Biopsy, Needle↗

Treatment of small cell lung cancer: the Copenhagen experience.

The present article is a review of recent treatment protocols for patients with small cell lung cancer (SCCL) treated in Copenhagen from 1985 to 1990. Furthermore, preliminary data on long-term survivors (> 5 years) from 9 treatment protocols since 1973 are reviewed. For 484 patients < or = 70 years old, no survival difference was observed between 2 platinum (cis-platinum or carboplatin) containing regimens, while the survival was better in these two induction regimens compared to an alternating control arm. For patients > 70 years old, Etoposide (VP-16) and Teniposide (VM-26) were compared in a randomized fashion. Both drugs were highly active, and no significant difference in activity was observed. All together 1527 patients have been included in clinical trials in the Copenhagen Lung Cancer Study Group since 1973. The rates of 5- and 10-years survivors were 3.5% and 1.8% respectively. Long-term survival can be achieved in all stages of SCCL.

Aged↗