1
134 Abstracts/Lung Cancer II (1994) 123-150 classification of early squamous lung cancer is pertinent for determioing the prognosis and selection of treatment. We emphasize that efforts be made to detect early lung cancer. Chromosome abnormalities in non-small cell lung cancer pleural effusion% Cytogenetic indicators of disease subgroup Lukeis R, Ball D, Irving L, Garsoo OM, Hasthorpe S. Cell Biology, Peter MacCallum Cancer Institute, Melbourne, Vie. 3lXX7. Genes Chromosomes Cancer 1993;8:262-9. A cytogenetic study of pleural eftitsions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adeo-inomas [ADC] including 1 giant cell variant) was performed to identify non- random chromosome abnormalities Numerical abnormalities seen in 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes4,9,10,13,15,16,18,19,21,and22.Tltemostfrequeot structural abnormality involved rearrangement in lp with breakpoints clustering at lplO-~13. other recurrent breakpoint regions, seen in 30% of cases, occurred in chromosome regions 3plO-p21,3qllq25, 6pll-~25, 6q13q23, 7qllq36, 9q32q34, llpll-~13, llq13- q24, 13~114~ and/or Hip, 17p and 19p, with, in particular, apparent loss of 6q21-q27,3p21-p26,7q2lq22,9p22-p24(shorteatregionsofcommon overlap)and 17~. Therewasalsorectnreotgainof lq23q44,8q13q24, and 1 lq13q23. These abnormalities were not restricted to a particular histological subtype, with the exception of + 8 and a breakpoint in 9q32- q34, which were seen only in ADC. The 9q32q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogeoetic differences between the two which may be associated with pleural invasion of NSCLC. Satellite PET and lung cancer: A prospective study in surgical patients Slosman DO, Spiliopoulos A, Couson F, Nicod L, Louis 0, Lemoine Ret al. Division ofNuclearMedicine, University Hospital, 1211 Geneve 14. Nucl Med Commun 1993;14:95561. Positron emission tomogmphy (PET) appears to be an innovative method for imaging the proliferative activity of malignant tissue, iu particular by means of ‘*F-labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was investigated in a satellite ceotre as an adjunct to cooventiooal methods for estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of detection of lung cancer in candidates was determined prior to exploratory or therapeutic thoracotomy by FDG PET imaging. Thestudy involved 36 patients with abnormal chest roeotgeoogram and suspected lung cancer who were due for thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively. Pulmonary malignancy was found in 31136 patients and 29 had a focal increase in FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three of whom had a negative PET scan. The sensitivity of detection of lung cancer by FDG PET was therefore 93.5 I. Bayesian study shows that FDG PET could be the most useful method in a population with a low prevalence of lung cancer. As illustrated by our study, a simple FDG PET scanning protocol in a satellite PET centra could provide adequate clinical information and help in deciding subsequent patient management. Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma Pujol J-L, Giboey DJ, Su JQ, Maksymiuk AW, Jett JR. Division of Medical Oncology, Mayo Clinic, 200 First St., SW, Rochester, MN 55905. J Nat1 Cancer Inst 1993;85: 1844-50. Backgroundz Chemotherapy, with or without radiotherapy, results ina30%-40% completerespooserateinsmpll-celllungcancer(SCLC), but approximately 90% of patients who have complete remission die within 2 years after relapse with chemoresistant disease. Randomized clinical studies of maintenance chemotherapy aBer complete response have failed to demonstrate survival advantage. However, studies have shown that the human cytokine interferon gamma (IFN-gamma) induces immune response in humans, including T-cell activation and expression of class II major histocompatibility complex (HLA- DR) and receptor for the Fc portion of immunoglobulin on mooocytes. It has also been demonstrated that recombinant IFN-gamma (rIFN-gamma) induces immuoomodulatioo and has anti-proliferative activity. Purpose: In vivo effects of rIFN-gamma treatment were characterixed by flow cytometric analysis of peripheral blood mononuclear cells in patieots with SCLC who received rIFN-gamma as maintenance treatment. Methoak After induction chemotherapy and radiotherapy, 100 patients who achieved a complete remission were randomly assigned to receive rIFN-gamma at a dose of 0.2 mg (4 x lo6 units) once a day, subcutaneously, for 6 months, or observation only. Jn 31 patients, peripheral mononuclear cells were obtained prior to tbe study and at weeks 4,8, and 12 for serial monitoring of immune response. By flow cytometric analysis, we ideotifiedthelymphocyteandmooocytepopulationsusiogcharacteristic differences in electronic volume and right-angle scatter. IO these populations, we determined the mean fluoreacencechannel after staining for CD14 (antigen expressed oo mooocytea), CD3 (antigen expressed on T lymphocytes), and HLA-DR (HLA class II expressed by mooocytes and activated lymphocytes). To determine the number of Fc receptors per cell, an Fc receptor assay was performed using the mooocyte cell line U937 as a standard. Results: At weeks 4,8, and 12, expression of HLA- DR and Fc receptors on mooocytes in patients who received rIFN- gamma was significantly higher than that in untreated patieots, and the difference was statistically significant. The number of Fc receptors per mooocyte consistently increased during the rIFN- gamma treatment and reached a fivefold elevation at week 12. There was oo statistically significant difference in lymphocyte surfaceantigen expressionbetween the treated and untreated groups. Conclusion: The dose of rIFN-gamma used in this study resulted in immune stimulation in patients with SCLC who had complete remission after induction therapy. The in vivo inununomodulatory activity of rIFN-gamma in such patients is characterized by a strong mooocyte activation but no significant alteration in T-cell activation. Bronchogenic cancer in patients under 40 years old: The experience of a Latin American country GreeaLS, Fortoul TI, Poociano G, Robles C, Riven, 0. Chest 1993;- 104:1477-81. Lung cancer in young patients is increasing in frequency, as documented by data from the United Statea, Canada, Japan, and European countries. However, to date and to our knowledge, there have not been any reports from Latin America on this topic. The published reports show that lung cancer in young patients is associated with smoking habit and family history of lung cancer. Its clinical course seems to be more aggressive than in older patients and the histologic type is less o&n squamous type. We describe 48 patients, aged 40 years or younger, who were diagnosed as having lung cancer in the Jnstituto National de Cancerologia from 1980 to 1990. The patients were equally divided between meo and women. Smoking was documented for only 46 percent of the cases. The histologic type most frequently diagnosed was adeoocarcinoma (N = 26) followed by squamous cell carcinoma (N = 12). Almost all the - (46 casea) were staged IV according to the TNM classification. A group of 33 patients older than 40 years (56 to 82 years) were used for comparison. The differences in sex ratio that were higher for men in the elder (m/f, 2.7: 1) were family history for cancer in six patients elder; positive smoking habit in all the aged

Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma

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134 Abstracts/Lung Cancer II (1994) 123-150

classification of early squamous lung cancer is pertinent for determioing the prognosis and selection of treatment. We emphasize that efforts be made to detect early lung cancer.

Chromosome abnormalities in non-small cell lung cancer pleural effusion% Cytogenetic indicators of disease subgroup Lukeis R, Ball D, Irving L, Garsoo OM, Hasthorpe S. Cell Biology, Peter MacCallum Cancer Institute, Melbourne, Vie. 3lXX7. Genes Chromosomes Cancer 1993;8:262-9.

A cytogenetic study of pleural eftitsions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adeo-inomas [ADC] including 1 giant cell variant) was performed to identify non- random chromosome abnormalities Numerical abnormalities seen in 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes4,9,10,13,15,16,18,19,21,and22.Tltemostfrequeot structural abnormality involved rearrangement in lp with breakpoints clustering at lplO-~13. other recurrent breakpoint regions, seen in 30% of cases, occurred in chromosome regions 3plO-p21,3qllq25, 6pll-~25, 6q13q23, 7qllq36, 9q32q34, llpll-~13, llq13- q24, 13~114~ and/or Hip, 17p and 19p, with, in particular, apparent loss of 6q21-q27,3p21-p26,7q2lq22,9p22-p24(shorteatregionsofcommon overlap)and 17~. Therewasalsorectnreotgainof lq23q44,8q13q24, and 1 lq13q23. These abnormalities were not restricted to a particular histological subtype, with the exception of + 8 and a breakpoint in 9q32- q34, which were seen only in ADC. The 9q32q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogeoetic differences between the two which may be associated with pleural invasion of NSCLC.

Satellite PET and lung cancer: A prospective study in surgical patients Slosman DO, Spiliopoulos A, Couson F, Nicod L, Louis 0, Lemoine Ret al. Division ofNuclearMedicine, University Hospital, 1211 Geneve 14. Nucl Med Commun 1993;14:95561.

Positron emission tomogmphy (PET) appears to be an innovative method for imaging the proliferative activity of malignant tissue, iu particular by means of ‘*F-labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was investigated in a satellite ceotre as an adjunct to cooventiooal methods for estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of detection of lung cancer in candidates was determined prior to exploratory or therapeutic thoracotomy by FDG PET imaging. Thestudy involved 36 patients with abnormal chest roeotgeoogram and suspected lung cancer who were due for thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively. Pulmonary malignancy was found in 31136 patients and 29 had a focal increase in FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three of whom had a negative PET scan. The sensitivity of detection of lung cancer by FDG PET was therefore 93.5 I. Bayesian study shows that FDG PET could be the most useful method in a population with a low prevalence of lung cancer. As illustrated by our study, a simple FDG PET scanning protocol in a satellite PET centra could provide adequate clinical information and help in deciding subsequent patient management.

Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma Pujol J-L, Giboey DJ, Su JQ, Maksymiuk AW, Jett JR. Division of Medical Oncology, Mayo Clinic, 200 First St., SW, Rochester, MN 55905. J Nat1 Cancer Inst 1993;85: 1844-50.

Backgroundz Chemotherapy, with or without radiotherapy, results

ina30%-40% completerespooserateinsmpll-celllungcancer(SCLC), but approximately 90% of patients who have complete remission die within 2 years after relapse with chemoresistant disease. Randomized clinical studies of maintenance chemotherapy aBer complete response have failed to demonstrate survival advantage. However, studies have shown that the human cytokine interferon gamma (IFN-gamma) induces immune response in humans, including T-cell activation and expression of class II major histocompatibility complex (HLA- DR) and receptor for the Fc portion of immunoglobulin on mooocytes. It has also been demonstrated that recombinant IFN-gamma (rIFN-gamma) induces immuoomodulatioo and has anti-proliferative activity. Purpose: In vivo effects of rIFN-gamma treatment were characterixed by flow cytometric analysis of peripheral blood mononuclear cells in patieots with SCLC who received rIFN-gamma as maintenance treatment. Methoak After induction chemotherapy and radiotherapy, 100 patients who achieved a complete remission were randomly assigned to receive rIFN-gamma at a dose of 0.2 mg (4 x lo6 units) once a day, subcutaneously, for 6 months, or observation only. Jn 31 patients, peripheral mononuclear cells were obtained prior to tbe study and at weeks 4,8, and 12 for serial monitoring of immune response. By flow cytometric analysis, we ideotifiedthelymphocyteandmooocytepopulationsusiogcharacteristic differences in electronic volume and right-angle scatter. IO these populations, we determined the mean fluoreacencechannel after staining for CD14 (antigen expressed oo mooocytea), CD3 (antigen expressed on T lymphocytes), and HLA-DR (HLA class II expressed by mooocytes and activated lymphocytes). To determine the number of Fc receptors per cell, an Fc receptor assay was performed using the mooocyte cell line U937 as a standard. Results: At weeks 4,8, and 12, expression of HLA- DR and Fc receptors on mooocytes in patients who received rIFN- gamma was significantly higher than that in untreated patieots, and the difference was statistically significant. The number of Fc receptors per mooocyte consistently increased during the rIFN- gamma treatment and reached a fivefold elevation at week 12. There was oo statistically significant difference in lymphocyte surfaceantigen expressionbetween the treated and untreated groups. Conclusion: The dose of rIFN-gamma used in this study resulted in immune stimulation in patients with SCLC who had complete remission after induction therapy. The in vivo inununomodulatory activity of rIFN-gamma in such patients is characterized by a strong mooocyte activation but no significant alteration in T-cell activation.

Bronchogenic cancer in patients under 40 years old: The experience of a Latin American country Greea LS, Fortoul TI, Poociano G, Robles C, Riven, 0. Chest 1993;- 104:1477-81.

Lung cancer in young patients is increasing in frequency, as documented by data from the United Statea, Canada, Japan, and European countries. However, to date and to our knowledge, there have not been any reports from Latin America on this topic. The published reports show that lung cancer in young patients is associated with smoking habit and family history of lung cancer. Its clinical course seems to be more aggressive than in older patients and the histologic type is less o&n squamous type. We describe 48 patients, aged 40 years or younger, who were diagnosed as having lung cancer in the Jnstituto National de Cancerologia from 1980 to 1990. The patients were equally divided between meo and women. Smoking was documented for only 46 percent of the cases. The histologic type most frequently diagnosed was adeoocarcinoma (N = 26) followed by squamous cell carcinoma (N = 12). Almost all the - (46 casea) were staged IV according to the TNM classification. A group of 33 patients older than 40 years (56 to 82 years) were used for comparison. The differences in sex ratio that were higher for men in the elder (m/f, 2.7: 1) were family history for cancer in six patients elder; positive smoking habit in all the aged