This seminar is based mainly on papers published during the past 5 years, although some classic papers have been cited. The search strategy selected articles from MEDLINE by use of the PubMed system. The key words used were “carcinoma, small cell lung” cross-referenced with key words such as “epidemiology”, “pathology”, “cytogenetics”, “molecular biology”, “diagnosis”, “antineoplastic agents”, “radiotherapy”, and “surgery”. Only papers with an abstract in English were considered.
SeminarSmall-cell lung cancer
Section snippets
Molecular biology
The specific sequence of genetic alterations leading to small-cell lung cancer is still unclear. However, several important genetic and molecular changes have been noted, including the identification of autocrine growth loops, proto-oncogene activation, and loss or inactivation of tumour-suppressor genes.
Presentation and diagnosis
Patients with small-cell lung cancer typically present with disseminated disease. Symptoms are related either to bulky, intrathoracic disease or to distant metastases; cough and dyspnoea are the most common findings (table 2).51 Small-cell lung cancer tends to be centrally located, with hilar masses and hilar and mediastinal adenopathy (figure 1). Bronchoscopy shows submucosal endobronchial lesions, which partly explain the low likelihood of finding tumour cells in cytological brushings or
Paraneoplastic syndromes
Small-cell lung carcinoma has long been associated with paraneoplastic syndromes. The endocrine paraneoplastic disorders are characterised by ectopic production of peptide hormones, and the neurological complications are related to antibody-mediated damage to the central nervous system (table 3).
Hyponatraemia can be found in up to 15% of patients with small-cell lung cancer at presentation.57 In many of these patients, ectopic production of antidiuretic hormone, also known as arginine
Staging
Patients with small-cell lung cancer rarely present with disease that is sufficiently localised for surgical resection to be possible, so the TNM staging system is generally not used. Instead, staging typically uses the Veterans Administration Lung Study Group system, which classifies patients as having either limited-stage or extensive-stage disease.75 The definition of limited-stage disease varies but is generally designed to include patients whose disease is limited to one hemithorax, with
Prognostic factors
Several pretreatment characteristics in patients with small-cell lung cancer have been associated with meaningful differences in survival that have also been noted in patients with non-small-cell lung cancer (panel).82, 83, 84, 85, 86 The identification of such factors allows physicians and investigators to compare different populations of patients and to interpret the contribution of treatment to differences in survival between different groups. For example, since women with small-cell lung
Treatment
Combination chemotherapy remains the cornerstone of treatment for both limited-stage and extensive-stage small-cell lung cancer. In general, the administration of etoposide and cisplatin plus chest radiotherapy for patients with good performance status and limited-stage disease should produce a complete-response rate of 80% or higher, median survival in excess of 17 months, and 5-year cancer-free survival of 12–25%.76, 87 Patients with extensive-stage disease given combination chemotherapy
Prophylactic cranial irradiation
Patients whose small-cell lung cancer has been successfully treated nonetheless have a 50–67% risk of developing metastases in the central nervous system.140, 141 Therefore, in patients who have had a complete response to chemotherapy, cranial irradiation is used prophylactically. The radiation is typically administered in doses of 24–46 Gy in eight to 15 fractions. A meta-analysis of randomised trials of prophylactic cranial irradiation showed that the intervention reduced the risk of brain
Search strategy and selection criteria
References (159)
- et al.
Lung cancer in Europe in 2000: epidemiology, prevention, and early detection
Lancet Oncol
(2003) - et al.
Effect of smoking cessation on major histologic types of lung cancer
Chest
(2001) - et al.
Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs
J Biol Chem
(1986) - et al.
Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells
J Biol Chem
(1991) - et al.
Clinical correlates of bombesin-like peptide receptor subtype expression in human lung cancer cells
Lung Cancer
(1996) - et al.
The FHIT gene 3p14.2 is abnormal in lung cancer
Cell
(1996) - et al.
Increasing use of bronchoscopic needle aspiration to diagnose small cell lung cancer
Mayo Clin Proc
(2000) - et al.
Systemic diseases associated with disorders of water homeostasis
Endocrinol Metab Clin North Am
(2002) - et al.
Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome
Lancet
(1989) - et al.
Value and accuracy of cytology in addition to histology in the diagnosis of lung cancer at flexible bronchoscopy
Respir Med
(2001)
Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus: ten-year follow-up
Lancet
Surgical treatment for limited small-cell lung cancer: the University of Toronto Lung Oncology Group experience
J Thorac Cardiovasc Surg
Influence of surgical resection prior to chemotherapy on the long-term results in small cell lung cancer: a study of 150 operable patients
Eur J Cancer Clin Oncol
The importance of surgical and multimodality treatment for small cell bronchial carcinoma
J Thorac Cardiovasc Surg
Radiation therapy for chest recurrences following induction chemotherapy in small cell lung cancer
Int J Radiat Oncol Biol Phys
The nature of the ‘oat-celled sarcoma’ of the mediastinum
J Pathol
Oat cell lung cancer
Cancer
Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress
J Clin Oncol
Cancer statistics, 2004
CA Cancer J Clin
Gender and histologic type variations in smoking-related risk of lung cancer
Epidemiology
Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung
J Clin Invest
Production of neuromedin B and neuromedin B gene expression in human lung tumor cell lines
Cancer Res
Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer
Nature
Phase I and imaging trial of a monoclonal antibody directed against gastrin-releasing peptide in patients with lung cancer
Clin Cancer Res
Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor
J Clin Oncol
Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer
Oncogene
Preferential expression of c-kit protooncogene transcripts in small cell lung cancer
Cancer Res
Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts
Br J Cancer
Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance
Clin Cancer Res
Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571
Oncogene
Imatinib mesylate efficiently achieves therapeutic intratumor concentrations in vivo but has limited activity in a xenograft model of small cell lung cancer
Clin Cancer Res
Phase II study of imatinib in patients with small cell lung cancer
Clin Cancer Res
A phase II NCCTG/CALGB trial of imatinib (STI571) in patients with c-kit-expressing relapsed small cell lung cancer (SCLC)
Proc Am Clin Soc Oncol
The role of c-myc in regulation of translation initiation
Oncogene
The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types
Anticancer Res
myc family DNA amplification in small cell lung cancer patients' tumors and corresponding cell lines
Cancer Res
myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens
Cancer Res
A combination treatment of c-myc antisense DNA with all-trans-retinoic acid inhibits cell proliferation by downregulating c-myc expression in small cell lung cancer
Antisense Nucleic Acid Drug Dev
Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene
J Clin Invest
Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays
Nat Biotechnol
The p53 tumour suppressor gene
Nature
Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer
Nature
Three distinct regions involved in 3p deletion in human lung cancer
Oncogene
FHIT as tumor suppressor: mechanisms and therapeutic opportunities
Cancer Biol Ther
Tumor suppressor RASSF1A is a microtubule-binding protein that stabilizes microtubules and induces G/M arrest
Oncogene
Unique anti-activator protein-1 activity of retinoic acid receptor beta
Cancer Res
Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells
Mol Cell Biol
Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells
Oncogene
Myristoylation of the fus1 protein is required for tumor suppression in human lung cancer cells
Cancer Res
Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression
J Natl Cancer Inst
Cited by (468)
Cell plasticity in patients with NSCLC: The controversial origins of transformed SCLC
2022, Biomedicine and PharmacotherapyNeuroendocrine neoplasms of the lung
2022, Practical Pulmonary Pathology: A Diagnostic ApproachLong-Term outcomes of intensity-modulated radiotherapy in limited-stage small-cell lung cancer classified according to AJCC 8th tumor node metastasis staging system
2024, European Review for Medical and Pharmacological Sciences