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NCI CANCERLIT^® Search: Small Cell Lung Cancer - September 2002

National Cancer Institute^®
Last Modified: September 1, 2002

Management of small cell lung cancer.
Hierarchical clustering of lung cancer cell lines using DNA methylation markers.
Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer.
Lung cancer in the elderly: current and future chemotherapeutic options.
A prospective study of a total material of lung cancer from a county in Sweden 1997-1999: gender, symptoms, type, stage, and smoking habits.
Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in
Elevated mortality from lung cancer associated with arsenic exposure for a limited duration.
Detection of MRP1 mRNA in human tumors and tumor cell lines by in situ RT-PCR.
To predict chemotherapy response using technetium-99m tetrofosmin and compare with p-glycoprotein and multidrug resistance related protein-1
Relationship between chemotherapy response of small cell lung cancer and P-glycoprotein or multidrug resistance-related protein expression.
Increased expression of integrin beta1 is a poor prognostic factor in small-cell lung cancer.
Comparison of changes in the NSE levels with clinical assessment in the therapy monitoring of patients with SCLC.
Whole-body 18F-2-deoxyglucose positron emission tomography in primary staging small cell lung cancer.
Treating small cell lung cancer.
Chemotherapy in advanced small lung cell cancer.
[The expression of P16 and Rb proteins in 106 cases of lung cancer]
Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer.
Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens.
NY-ESO-1 may be a potential target for lung cancer immunotherapy.
A randomized pilot study of SRL172 (Mycobacterium vaccae) in patients with small cell lung cancer (SCLC) treated with chemotherapy.
Dietary habits and lung cancer risk among Polish women.
Identical chemotherapy schedules given on and off trial protocol in small cell lung cancer: response and survival results.
Sentinel nodal assessment in patients with carcinoma of the lung.

1
UI - 11901913
AU - Johnson BE
TI - Management of small cell lung cancer.
SO - Clin Chest Med 2002 Mar;23(1):225-39
AD - Lowe Center for Thoracic Oncology, Department of Adult Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. bejohnson@partners.org
Small cell lung carcinoma typically presents as a central endobronchial lesion in chronic cigarette smokers with hilar enlargement and disseminated disease. The diagnostic pathology should be reviewed by a pathologist accomplished in reading pulmonary pathology, and, if any doubt exists in the diagnosis, additional special stains or diagnostic material should be obtained. Patients with extensive stage disease should be managed by combination chemotherapy, whereas patients with limited stage disease should be treated with etoposide/cisplatin plus concurrent chest irradiation. The chemotherapy should be administered for 4 to 6 months and then should be discontinued. Prophylactic cranial irradiation should be given to patients who achieve a complete remission. Patients should be retreated with chemotherapy if they develop a relapse of their small cell lung cancer. The patients who are followed in complete remission should be observed carefully for second cancers, and appropriate therapy should be administered if the cancer reappears.

2
UI - 11895880
AU - Virmani AK; Tsou JA; Siegmund KD; Shen LY; Long TI; Laird PW; Gazdar AF;
TI - Laird-Offringa IA Hierarchical clustering of lung cancer cell lines using DNA methylation markers.
SO - Cancer Epidemiol Biomarkers Prev 2002 Mar;11(3):291-7
AD - Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9593, USA.
Recent analyses of global and gene-specific methylation patterns in cancer cells have suggested that cancers from different organs demonstrate distinct patterns of CpG island hypermethylation. Although certain CpG islands are frequently methylated in many different kinds of cancer, others are methylated only in specific tumor types. Because distinct patterns of CpG island hypermethylation can be seen in tumors from different organs, it seems likely that histological subtypes of cancer within a given organ may exhibit distinct methylation patterns as well. The goal of our study was to determine whether the patterns of CpG island hypermethylation could be used to distinguish between different histological subtypes of lung cancer. We analyzed the methylation status of 23 loci in 91 lung cancer cell lines using the quantitative real-time PCR method MethyLight. Genes PTGS2 (COX2), CALCA, MTHFR, ESR1, MGMT, MYOD1, and APC showed statistically significant differences in the level of CpG island methylation between small cell lung cancer (SCLC) and non-small cell lung cancer cell lines (NSCLC). Hierarchical clustering using a panel consisting of these seven loci yielded two major groups, one of which contained 78% of the SCLC lines. Within this group, a large cluster consisted almost exclusively of SCLC cell lines. Our results show that DNA methylation patterns differ between NSCLC and SCLC cell lines and suggest that these patterns could be developed into a powerful molecular marker to achieve accurate diagnosis of lung cancer.

3
UI - 11207010
AU - Hrabec E; Strek M; Nowak D; Hrabec Z
TI - Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer.
SO - Respir Med 2001 Jan;95(1):1-4
AD - Department of Biochemistry, Institute of Physiology and Biochemistry, Medical University of Lodz, Poland. hrabec@lodz.cc
The 72 kDa matrix metalloproteinase (MMP-2) and the 92 kDa matrix metalloproteinase (MMP-9), are type IV collagenases that have been implicated as important factors in cancer invasion and metastasis formation. We have used quantitative zymography and computer-assisted image analysis to measure the levels of MMP-9 and MMP-2 in 19 samples of serum of lung cancer patients and in 23 samples of normal serum. Mean levels of MMP-9 were significantly elevated in cancer samples compared with normal sera (1.33 +/- 0.61 microU microl(-1) vs. 0.37 +/- 0.10 microU microl(-1), P<0.0001). MMP-2 levels did not differ significantly in these two groups. However, there was no significant correlation between serum MMP-9 activity and the disease stage. We found that circulation levels of MMP-9 in lung cancer patients is 3.6-fold higher than in healthy volunteers, however, we do not consider this elevation to be a direct reflection of MMP-9 over-production by tumour cells.

4
UI - 12093323
AU - Hinton S; Sandler A
TI - Lung cancer in the elderly: current and future chemotherapeutic options.
SO - Drugs Aging 2002;19(5):365-75
AD - Indiana University School of Medicine, Indianapolis, Indiana, USA.
Lung cancer is a prevalent malignancy disproportionately affecting the elderly, and in our aging societies will only increase in magnitude. Physicians typically assume that elderly lung cancer patients will have poorer prognoses. This belief is in part based on certain physiological changes of aging affecting the kidneys, liver, and bone marrow. However, there are no data to clearly support or refute increased toxicity from chemotherapy or a lessened therapeutic effect in the elderly based on these changes, although it is a field worthy of further study. Retrospective studies of treatment of elderly non-small cell and small cell lung cancer patients do not suggest a worse prognosis based on advanced age alone. Clinicians are hampered by the lack of clinical trials focusing on or even including the elderly, despite the increased incidence of lung cancer in the elderly. Phase II studies in elderly non-small cell lung cancer patients concentrate on newer agents (vinorelbine and gemcitabine) alone or combined with platinum compounds in hopes of more favourable toxicity profiles. Phase III trials have demonstrated survival benefits, quality of life improvements, and acceptable toxicity profiles for vinorelbine compared to best supportive care alone and the combination of vinorelbine and gemcitabine compared to vinorelbine alone. Data are also sparse for elderly small cell lung cancer patients. Phase II studies focused on single agent oral etoposide also in hopes of lessening toxicity. However, phase III trials have shown improvement in survival and quality of life for multiagent intravenous chemotherapy compared to oral etoposide. Given the existing data, altering therapy for lung cancer patients based on age alone would not be warranted. Given the prevalence of the disease, future studies need to include an appropriate number of elderly patients with continued emphasis on quality of life in addition to survival.

5
UI - 11891027
AU - Koyi H; Hillerdal G; Branden E
TI - A prospective study of a total material of lung cancer from a county in Sweden 1997-1999: gender, symptoms, type, stage, and smoking habits.
SO - Lung Cancer 2002 Apr;36(1):9-14
AD - Department of Respiratory Medicine, Gaevle County Hospital, S-801-87, Sweden. hirsh.koyi@lg.se
The epidemiology of lung cancer is changing in many parts of the world. In the industrialized countries, there is a trend that the incidence in men is declining, while it is increasing for women. Also, adenocarcinomas are becoming relatively more common, especially among men. The purpose of this study was to investigate whether such trends also occur in Sweden and also to describe other aspects of an unselected lung cancer material today, such as symptoms, stage and smoking habits. In the county of Gaevleborg, Sweden, practically all patients with lung cancer are referred to the lung department, and thus a total material of lung cancer patients with only a minimal selection bias can be studied. All patients with lung cancer in the county from January 1, 1997 to December 31, 1999, were investigated prospectively regarding stage, type of cancer, and symptoms. In all, there were 364 patients, 237 (65.1%) men and 127 (34.9%) women. The mean age for men was 69.8 and for women, 68.1 years. 91.9% of the men and 78.6% of the women were smokers or ex-smokers. In general the men were heavier smokers than were the women (P<0.0001). Adenocarcinoma was the most common subtype found in women and squamous cell carcinoma in men. The excess of adenocarcinoma in women was due to never-smoking women; for smoking and ex-smoking men and women, the proportion of adenocarcinomas was the same. In all, 240 patients (68.0%) were diagnosed at Stage IIIb (27.2%) or IV (40.8%), with no significant differences between the sexes. The most common first symptom was cough. Only 7.0% of patients were asymptomatic. In conclusion, the trend of an increasing proportion of adenocarcinoma in lung cancer is seen also in Sweden. A depressingly high percentage of patients present in late stages and are thus inoperable.

6
UI - 11863118
AU - Hanna NH; Sandier AB; Loehrer PJ Sr; Ansari R; Jung SH; Lane K; Einhorn
TI - LH Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study.
SO - Ann Oncol 2002 Jan;13(1):95-102
AD - Department of Medicine, Indiana University Medical Center, Indianapolis, USA. nhanna@iupui.edu
BACKGROUND: We performed this phase III study to determine whether the addition of 3 months of oral etoposide in non-progressing patients with extensive small-cell lung cancer (SCLC) treated with four cycles of etoposide plus ifosfamide plus cisplatin (VIP) improves progression-free survival (PFS) or overall survival. PATIENTS AND METHODS: Patients with extensive SCLC with a Karnofsky performance score (KPS) > or =50, adequate renal function and bone marrow reserve were eligible. Patients with CNS metastasis were eligible and received concurrent whole-brain radiotherapy. All patients received etoposide 75 mg/m2, ifosfamide 1.2 g/m2 and cisplatin 20 mg/m2 intravenously on days 1-4 every 3 weeks for four cycles. Non-progressing patients were randomized to oral etoposide 50 mg/m2 for 21 consecutive days every 4 weeks for three courses versus non-progressing patients subsequently randomized to oral etoposide (n = 72) or observation (n = 72). Minimum follow up for all patients is 2 years. Toxicity with oral etoposide was mild. There was an improvement in median PFS favoring the maintenance arm of 8.23 versus 6.5 months (P = 0.0018). There was a trend towards an improvement in median (12.2 versus 11.2 months), 1-year (51.4% versus 40.3%), 2-year (16.7% versus 6.9%) and 3-year (9.1% versus 1.9%) survival (P = 0.0704) favoring the maintenance arm. CONCLUSIONS: Three months of oral etoposide in non-progressing patients with extensive SCLC was associated with a significant improvement in PFS and a trend towards improved overall survival.

7
UI - 11911031
AU - Nakadaira H; Endoh K; Katagiri M; Yamamoto M
TI - Elevated mortality from lung cancer associated with arsenic exposure for a limited duration.
SO - J Occup Environ Med 2002 Mar;44(3):291-9
AD - Division of Social and Environmental Medicine, Department of Community Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan 951-8510. hiroto@med.niigata-u.ac.jp
In 1959, arsenic poisoning was detected in the town of Nakajo in Japan. The cause was exposure to inorganic arsenic in well water during 1954 to 1959. To examine the long-term effects of limited-duration arsenic exposure, we conducted mortality and survival studies for patients with chronic arsenic exposure and for control subjects from 1959 to 1992. The ratio of observed deaths to expected deaths from lung cancer was significantly high (7:0.64) for male patients. The lung cancer mortality rate was elevated markedly in subgroups with higher clinical severities of symptoms. Small cell carcinoma was specific to the exposed patients. The cumulative change of survival declined significantly in the exposed patients compared with the controls. The decline disappeared when lung cancer deaths were treated as lost to follow-up. The results showed that a 5-year period of arsenic exposure was associated with risk of lung cancer.

8
UI - 10964688
AU - Pascolo L; Fernetti C; Pirulli D; Bogoni S; Garcia-Mediavilla MV; Spano
TI - A; Puzzer D; Tiribelli C; Amoroso A; Crovella S Detection of MRP1 mRNA in human tumors and tumor cell lines by in situ RT-PCR.
SO - Biochem Biophys Res Commun 2000 Aug 28;275(2):466-71
AD - CSF-Department BBCM, University of Trieste, Via Giorgeri 1, Trieste, 34127, Italy.
The detection of the multridrug resistance-associated proteins is becoming increasingly important in assessing tumor sensitivity to treatment. In this work we describe a new, rapid, sensitive, and robust method for the detection of MRP1 expression based on direct RT-in situ-PCR technology and fluorochrome-modified (dCTP(Cy3)) nucleotides. MRP1 expression was found in both placenta (BeWo) and liver (Hep G2)-derived tumor cell line as well as in small cell lung carcinoma. In liver-derived cells, MRP1 expression was detected by RT-in situ-PCR but not by in situ hybridization, suggesting a higher sensitivity of in situ amplification for the low level of expression in Hep G2 cells. RT solution PCR confirmed the presence of MRP1 in BeWo and Hep G2 cells, although the level of the gene expression was lower in liver cells. This method represents a viable alternative to conventional immunohistochemistry, and may be useful in the evaluation of MRP1 expression in different tissue or cell lines. Copyright 2000 Academic Press.

9
UI - 11431107
AU - Shiau YC; Tsai SC; Wang JJ; Ho YJ; Ho ST; Kao CH
TI - To predict chemotherapy response using technetium-99m tetrofosmin and compare with p-glycoprotein and multidrug resistance related protein-1 expression in patients with untreated small cell lung cancer.
SO - Cancer Lett 2001 Aug 28;169(2):181-8
AD - Department of Nuclear Medicine, Far Eastern Memorial Hospital and Institute of Biomedical Engineering, College of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
The aim of this study was to investigate the relationships among technetium-99m tetrofosmin (Tc-TF) accumulation in untreated small cell lung cancer (SCLC), the expression of P-glycoprotein (Pgp) and multidrug resistance related protein-1 (MRP1), and the response to chemotherapy in patients with untreated SCLC. Thirty patients with SCLC were studied with chest scintigraphy 15 to 30 min after intravenous injection of Tc-TF before chemotherapeutic induction. Tc-TF chest scans were interpreted both visually and quantitatively. The response to chemotherapy was evaluated upon completion of chemotherapy. Immunohistochemical analyses were performed on multiple non-consecutive sections of biopsy specimens to detect Pgp and MRP1 expression. Fifteen patients with good response to chemotherapy had a significantly higher incidence (100.0%) of positive Tc-TF chest single photon emission computed tomography (SPECT) findings and negative Pgp or MPR expression than 15 patients with poor response (20%) (P<0.05). The tumor/background (T/B) ratios were 1.8+/-0.3 and 1.2+/-0.3 for patients with good response and poor response, respectively (P<0.05). However, other prognostic factors (performance status, tumor size and stage) were not significantly related to Tc-TF chest scan findings and response to chemotherapy. Tc-TF chest scintigraphy correlated well with Pgp or MRP1 expression and accurately predicted the response to chemotherapy in patients with SCLC.

10
UI - 12177731
AU - Hsia TC; Lin CC; Wang JJ; Ho ST; Kao A
TI - Relationship between chemotherapy response of small cell lung cancer and P-glycoprotein or multidrug resistance-related protein expression.
SO - Lung 2002;180(3):173-9
AD - Division of Pulmonary/Critical Care Medicine, China Medical College Hospital, Taichung, Taiwan.
The resistance of small cell lung cancer (SCLC) to anticancer drugs is a serious clinical problem often encountered during chemotherapy. Therefore, how to prevent this drug resistance need to be investigated. Multidrug resistance 1 (MDR1) gene and multidrug resistance-related protein (MRP) gene, two genes known to be associated with the development of drug resistance, are very common in SCLC. The purpose of this study was to evaluate retrospectively the relationship between chemotherapy responses to MDR1 gene encodes 170 kDa P-glycoprotein (Pgp) expression or MRP gene encodes 190 kDa MRP expression in SCLC. Before chemotherapy, multiple nonconsecutive sections of the bronchoscopy biopsy specimens of SCLC from 50 patients were analyzed immunohistochemically to detect Pgp and MRP expressions. Chemotherapy responses of the 50 patients were evaluated in the third month after completion of treatment by clinical and radiological methods. Of the 23 SCLC patients with poor response to chemotherapy, 11 had positive Pgp and MRP expressions, 2 had positive Pgp but negative MRP expressions, 6 had positive MRP but negative Pgp expressions, and 4 patients had negative Pgp and MRP expressions. All 27 SCLC patients with good response had negative Pgp and MRP expression. Immunohistochemical analyses of Pgp or MRP expression are potential tools for predicting patients' chemotherapy response in SCLC.

12
UI - 12168905
AU - Ebert W; Muley T; Trainer C; Dienemann H; Drings P
TI - Comparison of changes in the NSE levels with clinical assessment in the therapy monitoring of patients with SCLC.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1083-9
AD - Thoraxklinik Heidelberg gGmbH, Heidelberg Germany. prof.ebert@t-online.de
In a series of 130 consecutive patients suffering from small cell lung cancer (SCLC), we compared response evaluations according to standard criteria of the WHO with response evaluations according to changes in the neuron-specific enolase (NSE) levels during systemic therapy. For assessment by changes in the marker levels, the difference between two consecutive levels must exceed 30%. This value is based on the formula: Dc = 2(square root 2) x CV (CV: inter-assay coefficient of variation of the NSE test, set at 10 %). Of the 130 patients who entered this study, 18 patients received best supportive care and were excluded from the therapy monitoring. In the remaining 112 patients, 502 evaluations for response to therapy by both methods were performed, ie. 4.5 observations per patient. We found a concordance between the response evaluations according to the marker criteria and the clinical assessment in 69.7 % of the observations when including cases with positive lead-time and those with a temporary drop in the NSE levels due to a short-term response to therapy. The latter cases met the criteria consistent with the clinical evaluations at the next observation. The concordance with the clinical response evaluation increased to 84.2% when considering only those changes in the NSE levels where at least one of the consecutive marker levels was in the pathological range (> 14.5 ng/ml). Most discordant results were due to insufficient changes in the NSE levels at clinical remission or progression. A further limitation to the general use of NSE for therapy monitoring was founded on the marker negativity throughout the follow-up period, despite tumor progression or relapse. Changes in the levels between pretreatment NSE and after the first cycle of chemotherapy were shown to provide prognostic information. Patients with a drop in the NSE levels proved to have a significantly better survival probability than those with unchanging or rising marker values (p = 0.004). It is concluded that in the majority of evaluations, changes in the NSE levels are consistent with clinical findings based on imaging techniques but remain of doubtful utility in an individualpatient. NSE measurement can only be recommended as an adjunct to the clinical assessment in the follow-up of SCLC patients.

13
UI - 12168935
AU - Shen YY; Shiau YC; Wang JJ; Ho ST; Kao CH
TI - Whole-body 18F-2-deoxyglucose positron emission tomography in primary staging small cell lung cancer.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1257-64
AD - Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
The purpose of this study was investigate the role of 18F-2deoxyglucose positron emission tomography (FDG-PET) in staging small cell lung cancer (SCLC), its efficacy for the discrimination of limited disease (LD) and extensive disease (ED) stages and its regional sensitivity for different metastatic locations. Twenty-five patients with histologically confirmed SCLC and 42 radiologically-staged tumor sites were retrospectively investigated. The LD sample included 10 patients while the ED included 15 patients. All of the 25 primary tumor sites (100%) were visualized and 41 out of 42 (97.6%) of the metastases could be identified, but FDG-PET was needed for anatomical localization. The efficacy of FDG-PET was studied in the staging of SCLC patients and compared with the initial staging of conventional modality findings. FDG-PET down-staged (from ED to LD) one case and up-staged (from LD to ED) one case of SCLC. In summary, all of the patients with ED were correctly staged by FDG-PET alone. We conclude that FDG-PET is a substantial tool in the staging work-up of SCLC if it is performed initially to allow fast identification of patients with extensive disease stages and thus saves additional radiological or invasive examinations. Our preliminary results support the usefulness of whole body FDG-PET for staging SCLC.

14
UI - 1322215
AU - Von Eyben FE
TI - Treating small cell lung cancer.
SO - BMJ 1992 Jul 4;305(6844):53

15
UI - 8173389
AU - Ferry DR; Cullen MH
TI - Chemotherapy in advanced small lung cell cancer.
SO - BMJ 1994 Apr 2;308(6933):920

16
UI - 11372380
AU - Qin J; Chen G; Wang X
TI - [The expression of P16 and Rb proteins in 106 cases of lung cancer]
SO - Zhonghua Jie He He Hu Xi Za Zhi 2000 Oct;23(10):588-90
AD - Thoracic Department, Tianjin Thoracic Hospital, Tianjin 300051, China.
OBJECTIVE: To observe the relationship between the expression of P16 and Rb proteins and the proliferation of lung cancer cells. METHODS: The expressions of P16 and Rb proteins were measured in 66 cases of NSCLC and 40 cases of SCLC by means of immunohistochemistry technique. RESULTS: The inverse correlation of Rb and P16 proteins expression was confirmed in 66 cases of NSCLC (chi 2 = 10.52, P < 0.01). No relationship between the expression of P16 and differentiation, stage, lymph node metastasis or pathological type was found (P > 0.05). There was no correlation between the expression of Rb and differentiation, stage, lymph node metastasis or pathological pattern (P > 0.05). The frequency of the loss of Rb protein expression in SCLC (78%) was significantly higher than in NSCLC (21%, chi 2 = 32.3, P < 0.01). CONCLUSIONS: Loss of Rb protein expression in SCLC may be an important marker of the diagnosis of SCLC. The expression of P16 adversely correlates with that of Rb. This study provides strong confirmation about that there might be a negative feedback between P16 and Rb in phase G1.

17
UI - 11936538
AU - Brock CS; Lee SM
TI - Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer.
SO - Eur Respir J 2002 Mar;19(3):557-70
AD - Meyerstein Institute of Oncology, Middlesex/University College London Hospitals, UK. cbrock@icr.ac.uk
The generation of new blood vessels, angiogenesis, is important for tumour proliferation and metastasis. This involves a number of interacting processes and factors, such as growth factors and the receptor tyrosine kinases, matrix metalloproteinases and integrins. Studies have shown that tumour vascularity and the overexpression of growth factors and their receptors are of independent prognostic importance in different cancers, including lung cancer. The present article provides a background to angiogenesis and describes the potential targets for anti-angiogenic and vascular targeting strategies in cancer, focusing specifically on carcinoma of the lung. It also describes the anti-angiogenic drugs presently under phase I, II and III investigation and highlights some of the problems associated with the standard methodologies for assessing tumour response and drug efficacy using these agents.

18
UI - 12218575
AU - Nicholson SA; Beasley MB; Brambilla E; Hasleton PS; Colby TV; Sheppard
TI - MN; Falk R; Travis WD Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens.
SO - Am J Surg Pathol 2002 Sep;26(9):1184-97
AD - Department of Pulmonary and Mediastinal pathology, Armed Forces Institute of Pathology, Washington DC 20306-6000, USA.
Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.

19
UI - 10188057
AU - Lee L; Wang RF; Wang X; Mixon A; Johnson BE; Rosenberg SA; Schrump DS
TI - NY-ESO-1 may be a potential target for lung cancer immunotherapy.
SO - Cancer J Sci Am 1999 Jan-Feb;5(1):20-5
AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892-1502, USA.
PURPOSE: To evaluate the frequency of NY-ESO-1 expression in cultured lung cancer cells and to determine if this cancer-testis antigen can be presented for recognition by an HLA-restricted cytolytic T-cell clone specific for NY-ESO-1. METHODS AND RESULTS: Reverse transcriptase and polymerase chain reaction amplification techniques were utilized to screen a panel of lung and esophageal cancer cell lines for expression of NY-ESO-1 encoding a recently identified cancer-testis antigen. NY-ESO-1 expression was detected in 11 of 16 small cell lung cancer lines, three of seven non-small cell lung cancer lines, and zero of 12 esophageal cancer lines. 5-Aza-2' -deoxycytidine induced expression of NY-ESO-1 in lung cancer cells. Expression of HLA-A31 by plasmid transfection or retroviral transduction enabled recognition of lung cancer cells by an HLA-A31-restricted cytotoxic T lymphocyte clone specific for NY-ESO-1. CONCLUSIONS: NY-ESO-1 expression may be analogous to MAGE gene expression in lung cancer lines in terms of frequency and mechanism of transcriptional regulation. Furthermore, NY-ESO-1 can be presented on lung cancer cells for recognition by HLA-restricted cytotoxic T lymphocytes. Further investigation is warranted to determine if NY-ESO-1 can be exploited for the immunotherapy for lung cancer.

20
UI - 11899903
AU - Assersohn L; Souberbielle BE; O'Brien ME; Archer CD; Mendes R; Bass R;
TI - Bromelow KV; Palmer RD; Bouilloux E; Kennard DA; Smith IE A randomized pilot study of SRL172 (Mycobacterium vaccae) in patients with small cell lung cancer (SCLC) treated with chemotherapy.
SO - Clin Oncol (R Coll Radiol) 2002 Feb;14(1):23-7
AD - Royal Marsden Hospital NHS Trust, Sutton, Surrey, UK.
BACKGROUND: SRL172 is a suspension of heat killed Mycobacterium vaccae, that has been found to be a potent immunological adjuvant when used with autologous cells in animal models. This is a phase II study to test the clinical activity, feasibility and safety of combining SRL172 with chemotherapy to treat patients with small cell lung cancer (SCLC). METHODS: Patients were randomized to receive chemotherapy with (n=14) or without (n=14) SRL172. The chemotherapy was either platinum-based (MVP, n=10) or anthracycline-based (ACE, n=18). SRL172 was given intradermally on day 0, weeks 4, 8 and then 3-6 monthly. RESULTS: The treatment arms were well balanced for disease extent (43% with limited stage in each arm). The toxicity of chemotherapy and overall response at 12-15 weeks (57%) was the same for both treatment regimens. Median survival was 8.6 months and 12.9 for patients treated with chemotherapy alone and with the combination respectively (P=0.10). The survival trend was similar for both disease extent and chemotherapy regimen employed in favour of combination chemotherapy with SRL172. CONCLUSIONS: There is a trend to improved median survival in SCLC with the combination of chemotherapy and SRL172 with no increased toxicity and irrespective of drug regimen. A phase III study examining chemotherapy in combination with SRL172 in SCLC is now underway.

21
UI - 12234032
AU - Rachtan J
TI - Dietary habits and lung cancer risk among Polish women.
SO - Acta Oncol 2002;41(4):389-94
AD - Epidemiology Unit, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow, Poland. z5rachta@cyf-kr.edu.pl
The purpose of this case-control study was to examine the effect of usual diet, in relation to other risk factors, on the risk of different histologic types of lung cancer in women. A total of 242 women with histologically confirmed primary lung cancer and 352 healthy controls were enrolled in a study conducted in Cracow between 1991 and 1997. A multivariate analysis showed that frequent consumption of carrots (at least five times a week) significantly lowered the risk of lung cancer. The protective effects of carrots were statistically significant for squamous cell carcinoma, small cell carcinoma and adenocarcinoma. It was found that daily consumption of other vegetables had a significant protective effect against squamous cell carcinoma, and for all histologic types combined. Furthermore, a significantly reduced risk was observed in women who consumed margarine (at least three times a week). This effect was observed for all cell types. The results also suggest that frequent consumption of carrots and frequent consumption of margarine can have a protective influence against lung cancer irrespective of the number of cigarettes smoked and the amount of vodka drunk.

22
UI - 12189557
AU - Burgers JA; Arance A; Ashcroft L; Hodgetts J; Lomax L; Thatcher N
TI - Identical chemotherapy schedules given on and off trial protocol in small cell lung cancer: response and survival results.
SO - Br J Cancer 2002 Aug 27;87(5):562-6
AD - University Hospital Rotterdam, Department of Pulmonary Diseases. P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
Patients who are treated within clinical trials may have a survival benefit dependent on being a trial participant. A number of factors may produce such beneficial outcome including more rigorous adherence to a peer reviewed trial protocol, management by an experienced treatment team, being treated in a specialist centre etc. The current investigation compared patients treated on and off trial with the same standard arm treatment regimen. The results could then be interpreted without the confounding factors of differing treatment regimens, treatment teams or treatment hospitals. The results demonstrated given these circumstances that survival was no different for patients participating in a randomised trial compared with a group of patients similarly treated who were not eligible for trial entry or who declined randomisation. These results were obtained by the rigorous adherence to a defined protocol with the invaluable assistance of designated lung cancer staff.

23
UI - 12238853
AU - Schmidt FE; Woltering EA; Webb WR; Garcia OM; Cohen JE; Rozans MH
TI - Sentinel nodal assessment in patients with carcinoma of the lung.
SO - Ann Thorac Surg 2002 Sep;74(3):870-4; discussion 874-5
AD - Department of Surgery, Louisiana State University Health Sciences Center, New Orleans 70112, USA. fschmi@lsuhsc.edu
BACKGROUND: Assessment of sentinel nodes to predict metastases in a regional nodal basin is valuable for staging patients with melanoma and breast carcinoma. This study tested whether injection of isosulfan blue and technetium-99 could identify mediastinal sentinel nodes in patients with lung carcinoma and determine whether sentinel node histology predicts distal nodal metastases. METHODS: Isosulfan blue and technetium-99 were injected into the tumor and pulmonary resection performed. The hilum and mediastinum were assessed visually and with the gamma probe, and a mediastinal nodal dissection was performed. RESULTS: Thirty-one patients were evaluated. Three patients had positive sentinel nodes and positive distal mediastinal nodes. Twenty-two patients had negative sentinel nodes and negative distal nodes. No sentinel node was identified in 6 patients and 2 patients had two sentinel nodes. CONCLUSIONS: These data demonstrate that this rapid, simple technique can identify sentinel nodes in the mediastinum and that the sentinel node is an accurate predictor of distal nodal metastases in patients with lung cancer.

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