NCI CANCERLIT^® Search: Small Cell Lung Cancer - September 2001

Last Modified: November 1, 2001

Telediagnosis of transbronchial fine needle aspirations--a feasibility study.
Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation.
Expression of carcinoembryonic antigen in peripheral- or central-located small cell lung cancer: its clinical significance.
Paclitaxel in combination with carboplatin as salvage treatment in refractory small-cell lung cancer (SCLC): a multicenter phase II study.
[Immunomorphology of lymph nodes and prognosis in lung cancer]
Metallothionein expression in patients with small cell carcinoma of the lung: correlation with other molecular markers and clinical outcome.
Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1.
Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.

CancerMail from the National Cancer Institute

1
UI - 21236160
AU - Kayser K; Kayser G; Becker HD; Herth F
TI - Telediagnosis of transbronchial fine needle aspirations--a feasibility study.
SO - Anal Cell Pathol 2000;21(3-4):207-12
AD - Department of Pathology, Thoraxklinik, Heidelberg, Germany. klkayser@lung.de
AIM: To analyze the diagnostic accuracy of telediagnostic procedures for transbronchial fine needle aspirations. MATERIAL AND METHODS: A double blind study was performed on cytological slides of 54 randomly selected cases with transbronchial fine needle aspirations. The slides were digitized using a Leica digital camera DC100 mounted on a microscope Leica Laborlux S, and analyzed by an experienced pathologist without knowing the definite diagnosis or any additional clinical data. The diagnoses stated by analyzing the digital images were compared to the final conventional diagnoses. In addition, the duration of the digital diagnosis, used magnifications, and difficulties for correct sampling were documented. RESULTS: The "digital" diagnoses of the 54 cases were all in general agreement with the definite diagnoses. No wrong positive or wrong negative case in respect to malignant/non-malignant (31/23) or to small cell/non-small cell (9/22) occurred. The performance of a digital diagnosis lasted for 115 s at average (15-260 s), and is significantly longer compared to that of conventional fine needle aspiration judgement (20 s). The screening magnification was commonly set to x2.5, that for definite diagnostic analysis x40. Benign diseases (2 tuberculosis and 3 sarcoidosis cases) were correctly classified. CONCLUSIONS: Telepathology systems can probably be used for fine needle aspiration analysis without major diagnostic errors. Their use can improve the endoscopic sampling and avoid second anesthesia when missing the lesion of request during the first examination.

2
UI - 21401136
AU - Steele JP
TI - Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation.
SO - Semin Oncol 2001 Jun;28(3 Suppl 10):15-8
AD - Department of Medical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK.
Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18. Copyright 2001 by W.B. Saunders Company.

3
UI - 21410091
AU - Bandoh S; Fujita J; Ueda Y; Fukunaga Y; Dohmoto K; Hojo S; Yang Y; Yamaji Y; Takahara J; Ishida T
TI - Expression of carcinoembryonic antigen in peripheral- or central-located small cell lung cancer: its clinical significance.
SO - Jpn J Clin Oncol 2001 Jul;31(7):305-10
AD - First Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan. sbandoh@mailbox.kms.ac.jp
BACKGROUND: Small cell lung cancer (SCLC) has a higher percentage of hilar masses than other histological types of lung cancer. The primary site is usually adjacent to the hilum, but we often observe primary sites in the peripheral lung field. In this study, our objectives were to elucidate whether peripheral-located small cell lung cancer (PSCLC) is an independent entity and whether it differs clinically from central-located small cell lung cancer (CSCLC). METHODS: We reviewed the clinical and pathological features of 52 patients treated at Kagawa Medical University Hospital between 1987 and 1996 with a diagnosis of SCLC. We defined CSCLC as a tumor whose primary site is located in the segmental bronchi or more proximally and PSCLC as a tumor located distal to the subsegmental bronchi. Twenty-one PSCLC patients and 31 CSCLC patients were identified. Kaplan-Meier survival curves were constructed and comparisons were made between PSCLC and CSCLC by the log-rank test. The carcinoembryonic antigen (CEA) level was also evaluated in each group. RESULTS: Although the percentage of limited disease (LD) in the patients with PSCLC was higher than that in the patients with CSCLC, the 3-year survival rate of PSCLC tended to be worse than that of CSCLC (9% for patients with PSCLC and 29% for those with CSCLC). Survival curves of patients with PSCLC also tended to be worse than those of patients with CSCLC, not only in the limited disease group but also in the extensive disease (ED) group. In addition, the mean CEA value in patients with PSCLC was higher than that in patients with CSCLC (p < 0.001), whereas the neuron specific enolase (NSE) level was not significantly different between PSCLC and CSCLC. The median survival of patients with pretherapeutic CEA titers of > or =5 ng/ml was significantly shorter than that in patients with CEA levels <5 ng/ml. CONCLUSION: These findings suggest that the survival of SCLC patients with a high CEA level was significantly shorter than that of patients with a low CEA level. In addition, CEA levels in PSCLC patients were significantly higher than those in CSCLC patients. However, the survivals of LD or ED patients with PSCLC and CSCLC were not statistically different.

4
UI - 21193594
AU - Kakolyris S; Mavroudis D; Tsavaris N; Souglakos J; Tsiafaki P; Kalbakis K; Agelaki S; Androulakis N; Georgoulias V
TI - Paclitaxel in combination with carboplatin as salvage treatment in refractory small-cell lung cancer (SCLC): a multicenter phase II study.
SO - Ann Oncol 2001 Feb;12(2):193-7
AD - Department of Clinical Oncology, University General Hospital of Heraklion, Crete, Greece.
PURPOSE: The activity and toxicity of paclitaxel plus carboplatin combination in patients with disease progression after initial chemotherapy for small-cell lung cancer (SCLC) was investigated in a multicenter phase II study. PATIENTS AND METHODS: Thirty-two patients (twenty-seven men) with extensive stage refractory SCLC after EP or CAV front-line chemotherapy were treated with paclitaxel 200 mg/m2 on day 1 and carboplatin 6 AUC on day 2 in a four-week schedule. The patients' median age was 60 years and the performance status (WHO) was 0 for 9, 1 for 20 and 2 for 3 patients. All patients were evaluable for toxicity and 29 for response. RESULTS: Complete response was observed in one (3%) and partial response in seven (22%) for an overall response rate of 25% (95% confidence interval (CI): 10%-40%). Seven (22%) patients had stable disease and seventeen (53%) progressive disease. All but one of the responders had been previously treated with EP combination and three of them had failed to respond. The median duration of response and the median TTP were 3 and 5.5 months, respectively. The median overall survival was seven months. Grade 3-4 neutropenia was observed in 12 (37%) patients and in 2 of these it was associated with infection. There were no toxic deaths. Grade 4 anaemia was observed in one (3%) patient and grade 3 thrombocytopenia in three (9.4%). Non-hematologic toxicity was very mild with grade 2-3 asthenia occurring in 10 (25%) patients; asthenia was the reason for treatment discontinuation in 3 patients. CONCLUSIONS: The combination of paclitaxel and carboplatin is a relatively active and well-tolerated regimen as salvage treatment in patients with refractory SCLC.

5
UI - 21251183
AU - Di Giorgio A; Sammartino P; Canavese A; Arnone P; Sibio S; Accarpio F; Al Mansour M
TI - [Immunomorphology of lymph nodes and prognosis in lung cancer]
SO - Minerva Chir 2001 Apr;56(2):153-9
AD - Dipartimento di Chirurgia Pietro Valdoni, Universita degli Studi La Sapienza, Rome, Italy.
BACKGROUND: Many studies have investigated locoregional immune responses and long-term survival in various types of cancer; few have focused on lung cancer. This study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes in patients resected for bronchogenic carcinoma. METHODS: In a retrospective analysis, immune responses in locoregional lymph nodes were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al.: sinus histiocytosis (SH) and paracortical lymphoid cell hyperplasia (PCA) were considered as a cellular immune response, and follicular hyperplasia of the cortical area (CA) as a humoral reaction. The survival rate was estimated by the Kaplan-Meier product-limit method. Log-rank test and Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analysis. RESULTS: 35.5% of the patients had no evident response in regional nodes; 19.8% had a marked cellular response; 11% a marked humoral response; and 33.7% a mixed cellular-humoral response. A nodal cellular response improved long-term survival rates even in patients with regional node metastases. Multivariate analysis identified an independent variable as having high prognostic value: lymph node immunoreactivity. CONCLUSIONS: Lymph node immunoreactivity significantly influences long-term survival after curative surgery for lung cancer and may be useful in stratifying patients for prospective trials of adjuvant treatment including immunotherapy.

6
UI - 21433643
AU - Joseph MG; Banerjee D; Kocha W; Feld R; Stitt LW; Cherian MG
TI - Metallothionein expression in patients with small cell carcinoma of the lung: correlation with other molecular markers and clinical outcome.
SO - Cancer 2001 Aug 15;92(4):836-42
AD - Department of Pathology, University of Western Ontario, London, Ontario, Canada. mariamma.joseph@sjhc.london.on.ca
BACKGROUND: Patients with small cell carcinoma of the lung (SCLC) are known to have an extremely poor prognosis, with a 5-year survivor rate of only 5%. Chemotherapeutic drug resistance is a major obstacle to curative therapy in patients with SCLC. METHODS: The authors evaluated retrospectively the expression of metallothionen (MT), proliferating cell nuclear antigen (PCNA), p53, and retinoblastoma gene product (RBGP) in biopsy samples from 58 patients with SCLC prior to standard chemotherapy. The objective was to study the correlation between MT and other molecular markers in SCLC and correlate these data with the clinical outcome of patients. The authors studied 28 short-term survivors (STS; survival < 24 months) and 30 long-term survivors (LTS; survival > 24 months). RESULTS: In line with expectations, the authors found a strong inverse association between stage and survival. Of 58 patients with SCLC, 26 patients (45%; 17 STS and 9 LTS) showed MT expression, 55 patients (94%; 28 STS and 27 LTS) were positive for PCNA, 28 patients (48%; 16 STS and 12 LTS) were positive for p53, and only 6 patients (10%; 1 STS and 5 LTS) showed positivity for RBGP. On comparing the percent positivity of various markers in the two survivor groups, there was greater frequency of expression of MT, PCNA, and p53 and lower RBGP expression in the STS group compared with the LTS group. However, only the difference in expression of MT between the two survivor groups was statistically significant (Fisher exact test; P = 0.034). Multivariable analysis using a logistic regression model showed a significant association between MT expression and patient survival after adjusting for disease stage (chi-square test; P = 0.022). There was also a statistically significant association between MT expression and p53 expression (chi-square test; P = 0.001). CONCLUSIONS: In this study, of the molecular markers studied, the authors demonstrated that only MT overexpression was independently predictive of short-term survival in patients with SCLC undergoing chemotherapy. Copyright 2001 American Cancer Society.

7
UI - 21424093
AU - Leech SN; Kolar AJ; Barrett PD; Sinclair SA; Leonard N
TI - Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1.
SO - J Clin Pathol 2001 Sep;54(9):727-9
AD - Department of Dermatology, Dryburn Hospital, North Road, Durham DH1 5TW, UK.
AIM: To investigate whether immunohistochemical staining for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) is useful in distinguishing Merkel cell carcinomas (MCCs) from metastatic small cell carcinomas (SCCs). METHODS: Eleven cases of MCC and 10 of lung SCC were stained for CK20 and TTF-1. RESULTS: Ten of 11 MCCs stained with the antibody to CK20. None was positive for TTF-1. No SCC stained with anti-CK20 and all stained strongly with anti-TTF-1. CONCLUSIONS: The use of both anti-CK20 and anti-TTF-1 can reliably distinguish between MCC and metastatic SCC, thus avoiding the need for a detailed clinical investigation of patients with MCC in whom metastatic SCC must be excluded.

8
UI - 20404015
AU - Virmani AK; Rathi A; Zochbauer-Muller S; Sacchi N; Fukuyama Y; Bryant D; Maitra A; Heda S; Fong KM; Thunnissen F; Minna JD; Gazdar AF
TI - Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.
SO - J Natl Cancer Inst 2000 Aug 16;92(16):1303-7
AD - Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75390-8593, USA.
BACKGROUND: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARbeta gene in human lung tumors and cell lines. METHODS: Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction. RESULTS: The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P:<.001). By contrast, in 57 of 58 control samples, we observed only the unmethylated form of the gene. Four tumor cell lines with unmethylated promoter regions expressed both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'-deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in 100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the difference was statistically significant (two-sided P: =.028). CONCLUSIONS: Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2 and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical demethylation is a potential approach to lung cancer therapy.