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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials of carbon beam radiotherapy for stage I non-small cell lung cancer (NSCLL), and their results, are briefly described. The local control rate, cause-specific and overall survival rates of 146 patients with clinical stage I NSCLC were 82.0%, 59.0% and 59.0%, respectively. Radiation pneumonia was not serious and infrequent (2.1%). In the phase II clinical study, the local control rate of 50 patients was 100% without radiation pneumonia, resulting in a 74.0% overall survival rate. Carbon beam therapy could be an alternative to surgery, especially for lung cancer patients of advanced age and/or with complications. For locally advanced lung cancer treated with carbon beams, excellent local control as in stage I NSCLC has been demonstrated, providing hopeful prospects for the treatment of lung cancer.
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PMID:[Heavy ion therapy for non-small cell lung cancer--new, radical radiotherapy for advanced-age patients as an alternative to surgery]. 1261 Aug 68

Among patients with non-small-cell lung cancer (NSCLC), those with pathological stage I have the best expectation of survival; however, survival is reduced to less than 50% in the long term. At present, it is unclear when patients can be reasonably defined as cured, and if they experience a higher incidence of malignant/nonmalignant diseases and a lower expectation of survival than the general population. A total of 134 stage I NSCLC patients, who had undergone resection at the Thoracic Surgery Unit of the General Hospital of Verona (north-eastern Italy) from October 1987 to December 1993, were still disease-free at 5 years. These subjects were further followed up, and morbidity and mortality rates were compared with those recorded in the general population of the same geographical area. The standardised incidence ratios (SIRs) for all malignancies and for lung cancer were higher than expected (2.39, 95% CI=1.6-3.5, P<0.001; 10.1, 95% CI=6.2-15.6, P<0.0001, respectively). The standardised mortality ratio (SMR) was also significantly increased (1.73, 95% CI=1.1-2.6, P=0.013). The excess mortality could be entirely explained by an increase in mortality from lung cancer (5.7, 95% CI=2.8-10.1, P<0.0001). This study shows that patients, resected for pathological stage I NSCLC and tumour-free after 5 years, have a higher incidence of new lung cancer compared with the general population, which in turn determines an excess in all-cause mortality in the following years.
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PMID:Persistent excess mortality from lung cancer in patients with stage I non-small-cell lung cancer, disease-free after 5 years. 1277 77

Most information on results with radiotherapy (RT) for stage I non-small cell lung cancer (NSCLC) is based on retrospective studies on RT-treated inoperable NSCLC cases. Thus, the role of RT for stage I NSCLC, as a curative modality, has not yet been established. A literature search for studies on stage I non-small cell lung carcinoma (NSCLC) treated by RT alone resulted in 18 papers published between 1988 and 2000. The majority of stage I patients received RT treatment because they were medically inoperable. The main contraindications for surgery were grave impairment of pulmonary function and serious cardiovascular disease. Local recurrence was the most common reason for treatment failure (median value 40%) but varied highly between the studies, ranging from 6.4 to 70%. In contrast with local recurrence, regional failure was not a major problem (0-3.2%). Generally, smaller tumour size, low T-stage and increased dose had a favourable impact on local control and increased local control was followed by increased survival. No serious treatment complications were recorded in the majority of these studies. Overall treatment results were, however, disappointing. The median survival in these studies ranged from 18 to 33 months. The 3- and 5-year overall survival was 34+/-9 and 21+/-8% (mean value+/-1 S.E.), respectively. The cause-specific survival at 3 and 5 years was 39+/-10 and 25+/-9% (mean value+/-1 S.E.), respectively. Dose escalation, in a setting with conformal RT using involved field or stereotactic RT, should be the focus of developmental therapeutic strategies with inoperable stage I NSCLC to improve local control and survival.
Lung Cancer 2003 Jul
PMID:The role of radiotherapy in treatment of stage I non-small cell lung cancer. 1282 6

Debate continues regarding the choice of resection for peripheral stage I (T1N0M0) non-small cell lung cancer (NSCLC). Anatomic lobectomy has been considered the standard of care for resectable NSCLC; however, intriguing results of clinical trials have been reported with the use of sublobar resection as primary therapy of selected small peripheral lung cancers. Most modern clinical studies comparing lobectomy to sublobar resection of stage I NSCLC demonstrate equivalent survival, but local recurrence following sublobar resection appears to be greater. Low energy computed tomography screening programs for lung cancer have increasingly identified small peripheral lesions potentially amenable to effective therapeutic management with sublobar resection. We discuss the possible management scenarios for stage I NSCLC in this age of early computed tomography detection of lung cancer, more precise molecular biologic staging of the disease, optimized peri-operative management of the marginally resectable patient, and improved adjunctive treatment measures for local control following lung cancer resection.
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PMID:Clinical trials of peripheral stage I (T1N0M0) non-small cell lung cancer. 1471 Mar 84

Human telomerase reverse transcriptase is a ribonucleoprotein that synthesises telomeric sequences, which decrease at each cell division. In cancer cells, its activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. To evaluate the prognostic value of the catalytic subunit telomerase reverse transcriptase (hTERT), we analysed its expression by immunohistochemistry in 122 formalin-fixed lung tumours including 42 squamous cell carcinoma (SCC), 43 adenocarcinoma (ADC), 19 basaloid carcinoma (BC) and 18 small-cell lung carcinoma (SCLC) in comparison with detection of hTERT mRNA by in situ hybridisation and relative telomerase activity by TRAP assay in a subset of tumours. We observed a high concordance between hTERT protein expression and detection of hTERT mRNA and telomerase activity. Telomerase expression varied according to histology (P=0.0002) being significantly lower in ADC than in SCC, BC and SCLC (P<0.0001). Adenocarcinoma and SCC exhibited either a nuclear or a nucleolar staining in contrast with a diffuse nuclear staining observed in most BC and all SCLC (P=0.01). In stage I NSCLC telomerase expression was lower than in other stages (P=0.04), and a nucleolar staining was correlated with a short survival (P=0.03). We concluded that telomerase expression and pattern are distinctive among histopathological classes of lung cancer and convey prognostic influence.
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PMID:Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours. 1502 5

We have developed a novel irradiation technique for lung cancer that combines a linear accelerator and CT scanner with patient-controlled breath-hold and radiation beam switching. We applied this technique to stereotactic three-dimensional (3D) conformal radiotherapy for stage I non-small cell lung cancer (NSCLC) and evaluated the primary therapeutic outcomes. A total of 35 patients with stage I (15 IA, 20 IB) primary NSCLC (20 adeno, 13 squamous cell, and 2 others) were treated with this technique. Patients ranged from 65 to 92 years old (median, 78 years). Twenty-three (66%) patients were medically inoperable due to mainly chronic pulmonary disease or high age. Three-dimensional treatment plans were made using 10 different non-coplanar dynamic arcs. The total dose of 60 Gy was delivered in 10 fractions (over 5-8 days) at the minimum dose point in the planning target volume (PTV) using a 6 MV X-ray. After adjusting the isocenter of the PTV to the planned position by a unit comprising CT and linear accelerator, irradiation was performed under patient-controlled breath-hold and radiation beam switching. All patients completed the treatment course without complaint. Complete response (CR) and partial response (PR) rates were 8/35 (23%) and 25/35 (71%), respectively. Pulmonary complications of National Cancer Institute-Common Toxicity Criteria grade >2 were noted in three (9%) patients. During follow-up (range, 6-30 months; median, 13 months), two (6%) patients developed local progression and five (14%) developed distant or regional lymph node metastases. Two-year overall survival rates for total patients and medically operable patients were 58 and 83%, respectively. In conclusion, this new irradiation technique, utilizing patient-controlled radiation beam switching under self-breath-hold after precise alignment of the isocenter, allows safe high-dose stereotactic radiotherapy with sufficient margins around the CTV and reduced treatment times. Based on the initial results, excellent local control with minimal complications is expected for stage I NSCLC.
Lung Cancer 2004 Jul
PMID:Clinical outcomes of stereotactic radiotherapy for stage I non-small cell lung cancer using a novel irradiation technique: patient self-controlled breath-hold and beam switching using a combination of linear accelerator and CT scanner. 1519 34

Expression of insulin-like growth factor-binding protein-3, which (IGFBP-3) inhibits the proliferation of non-small-cell lung cancer (NSCLC) cells by inducing apoptosis, is lost in about half of stage I NSCLC cases. Since promoter methylation can silence gene expression, we investigated whether hypermethylation of the IGFBP-3 promoter is involved in loss of IGFBP-3 expression in NSCLC. We found the IGFBP-3 promoter to be methylated in seven of 13 NSCLC cell lines and in 16 of 23, seven of 9, eight of 11, and six of six tumor specimens from patients with stage I, II, III, and IV NSCLC, respectively. Methylation status correlated with IGFBP-3 mRNA and protein levels in a subset of NSCLC cell lines tested in our study. However, treatment with 5'-aza-2'-deoxycytidine (5'-aza-dC) restored IGFBP-3 expression in four of seven NSCLC cell lines with the methylated promoter, suggesting that multiple mechanisms regulate IGFBP-3 expression in NSCLC. Gel shift and chromatin immunoprecipitation assays showed that methylation of the Sp-1/Sp-3-binding element in the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG-binding protein-2 (MeCP2), and histone deacetylase (HDAC). A luciferase construct expressing IGFBP-3 promoter in which the Sp-1/Sp-3 binding element was methylated showed significantly reduced transcriptional activity. The reduction in promoter activity was further suppressed by overexpression of MeCP2, which was rescued by 5'-aza-dC. Thus interference with Sp-1 transactivation by MeCP2 may contribute to the transcriptional defect of IGFBP-3 expression in NSCLC cells with methylated promoter.
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PMID:Mechanisms underlying lack of insulin-like growth factor-binding protein-3 expression in non-small-cell lung cancer. 1524 4

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.
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PMID:Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung. 1538 24

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.
Lung Cancer 2005 Apr
PMID:Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer. 1577 77

S100A2, a calcium-binding protein, recently became of major interest because of its differential expression during transformation and metastasis in various tumors. The purpose of this study was to investigate the prognostic significance of S100A2 expression in the early-stage non small lung cancer (NSCLC). Immunohistochemical analysis to determine the percentage of cells staining positive for S100A2 was performed on 11 NSCLC tissue microarray slides containing samples from 113 patients with pathologic stage I NSCLC who had undergone curative surgery. S100A2 was expressed in samples from 79 patients (69.9%). Kaplan-Meier analysis showed that patients whose tumors had positive S100A2 expression had a significantly lower overall survival and disease-specific survival rate at 5 years after surgery than did patients with negative S100A2 expression (p < 0.001 and p < 0.001, respectively). Age at diagnosis, histologic type of cancer, degree of differentiation and smoking history did not have a statistically significant effect on survival. Multivariate analysis confirmed that S100A2 expression is a better predictor for disease-specific survival than were other clinical and histologic variables tested. Our results suggested that the expression of the S100A2 protein in stage I NSCLC indicates poor prognosis and may be used to identify patients with early-stage NSCLC who might benefit from adjuvant treatment.
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PMID:Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer. 1580 Sep 16


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