Biomedical subjects

M Paesmans

Publications and source records attributed to M Paesmans.

At least 19 recordsLinked to original sources

PubMed2007

Acute confusion in patients with systemic cancer.

OBJECTIVE: To determine the incidence, the causes and the prognostic value for survival of acute confusion (delirium) in patients admitted to a general cancer hospital. PATIENTS: Hundred consecutive patients with confusion were examined; 78 had a metastatic disease, 11 had local tumor and 11 had no sign of tumor recurrence at admission. Patients with confusion represented 11.8% (95%CI: 9.7-14.2%) of admissions. Follow-up period lasted 18 months from the inclusion of the last patient. RESULTS: Structural brain lesions (SBL) were mostly metastatic and caused confusion in 36 patients. 57 patients had a toxic or metabolic encephalopathy (TME). The cause remained unexplained in 6 cases, and in one patient the final diagnosis was psychotic state. Most patients with TME had more than one abnormality which could cause confusion. Confusion was reversible in 34 patients, and the odds for its regression was 3-fold higher in patients with TME (P = 0.02). Survival was significantly shorter (P = 0.02) in patients with SBL (median: 3 weeks) than in patients with TME (median: 8 weeks). However, the survival was significantly longer (P = 0.007) in patients with only one toxic or metabolic disorder (median: 20.5 weeks) than in patients with multiple changes (median: 5 weeks). CONCLUSION: Confusion is common in general cancer population. TME is the leading etiology and it is due to multiple causes in most patients. SBL causes confusion in one third of the patients. Patients with TME have a greater chance to recover, and survive longer especially if they have only one toxic or metabolic change.

Adult↗

PubMed2006

Thyroid transcription factor 1--a new prognostic factor in lung cancer: a meta-analysis.

BACKGROUND: The aim of this study was to determine the prognostic role for survival of thyroid transcription factor 1 (TTF-1) in lung cancer. METHODS: Studies evaluating survival and TTF-1 in lung cancer patients, published until August 2005, were assessed with a methodological scoring system. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and a combined HR was calculated. RESULTS: We identified 10 eligible papers, all dealing with non-small-cell lung cancer (NSCLC). Eight were meta-analysed (evaluable studies). Seven studies included patients with local and/or locoregional diseases and three dealt only with adenocarcinoma. Median methodological quality score was 65.9% (range = 31.8%-70.5%). TTF-1 positivity was associated with statistically significant reduced or improved survival in one and four studies, respectively. Combined HR for the eight evaluable studies was 0.64 [95% confidence interval (CI) = 0.41-1.00]. In the subgroup of adenocarcinoma, the combined HR was 0.53 (95% CI = 0.29-0.95). CONCLUSION: TTF-1 is a good prognostic factor for survival in NSCLC. Its effect appears also significant when the analysis is restricted to patients with adenocarcinoma. This study supports the fact that TTF-1 could be included in further prospective trials studying prognostic factors in NSCLC.

Humans↗

PubMed2006

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results.

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.

Humans↗

PubMed2006

Causes of fever in cancer patients (prospective study over 477 episodes).

GOALS OF WORK: The aim of this study was to determine the causes of fever among cancer patients. METHODS: All febrile cancer patients were followed up prospectively. Clinical, microbiological and radiological documentations were performed. Aetiologies of fever, type of tumour, site of infection, type of microorganism and outcome were assessed and compared between neutropenics and non-neutropenics. RESULTS: Four hundred and seventy-seven episodes were evaluated. Infection, non-infectious causes and fever of unknown origin represented 67, 23 and 10%, respectively. The respiratory tract is the most frequently involved site in infection (29%), and in microbiologically documented infections, Gram-negative bacilli were predominant. The tumour itself (27%) or an invasive procedure (17%) were the main causes of non-infectious febrile episodes. Mortality from infection was higher among non-neutropenic (11.1%) than neutropenic patients (4.3%). CONCLUSION: Fever in cancer patients remains a challenge, and the differentiation between infectious and non-infectious causes at onset of fever is very difficult. Despite all the prophylactic measures, infection is still the principal cause. However, the infection-related mortality is low either in neutropenic or non-neutropenic patients.

Belgium↗

PubMed2006

Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients.

Combination therapy with a beta-lactam plus an aminoglycoside has been the standard approach for treating febrile neutropenia for many years. More recently, beta-lactam monotherapy has also been shown to be a reliable and safe approach. In the present study, 763 eligible patients with fever and neutropenia received piperacillin-tazobactam monotherapy. On day 3, according to the study protocol, 165 patients with persistent fever who fulfilled the study entry criteria were randomised to receive vancomycin or a placebo. The success rate was 51% in the intention-to-treat analysis and 62% in the per-protocol analysis. The overall mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the initial or subsequent infection. Randomisation had no influence on the study endpoints. The adverse event rate was evaluated only in the patient population not included in the randomised part of the study. Among these patients, adverse events probably or definitely related to piperacillin-tazobactam therapy were uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It was concluded that piperacillin-tazobactam could be considered as monotherapy for patients with high-risk febrile neutropenia.

Adolescent↗

PubMed2005

Can we predict the duration of chemotherapy-induced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis.

BACKGROUND: The aim of the study was to elaborate a predictive model for the duration of chemotherapy-induced neutropenia (CIN) allowing the identification of patients with a higher risk of complications, especially complicated febrile neutropenia, who might benefit from preventive measures. PATIENTS AND METHODS: A score ranging from 0 to 4 on the basis of expected CIN was attributed to each cytotoxic agent given as part of chemotherapy treatment in solid tumours for patients with febrile neutropenia (FN). The individual scores were combined into several overall scores. RESULTS: A total of 203 patients with FN were eligible for this retrospective analysis. We were able to identify two groups of patients with statistically different neutropenia durations with median durations until hematological recovery of ANC > or =0.5 and > or =1.0 x 10(9)/l, being respectively 6 versus 4 days (P = 0.03) and 8 versus 6 days (P = 0.01). CONCLUSIONS: The duration of neutropenia is directly influenced by the aggressiveness of the chemotherapy regimen. In this retrospective study, we were able to identify a group of patients who needed two more additional days to recover from grade 3 and grade 4 neutropenia, based on the degree of aggressiveness of the cytotoxic agents used.

Adolescent↗

PubMed2005

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16-1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26-2.02) and in studies using PCR (HR 1.40; 95% CI 1.18-1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86-1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant chemotherapy: results of a meta-analysis of the literature.

The recent publication of many randomised trials about (neo)adjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC) has prompted our group to update a prior meta-analysis of the literature. Randomised studies published in French and English between 1965 and June 2004 were included in this analysis. A qualitative assessment of each trial was first performed using the European lung cancer working party (ELCWP) and the Chalmers' scales. In absence of statistically significant quality difference between positive and negative trials, a quantitative aggregation (meta-analysis) of the individual results was performed. Two trials for which data were available on ASCO virtual meeting website were also included in the meta-analysis. Twenty-five studies eligible for this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery (n = 19). No quality difference was detected between positive and negative trials according to the two scores, whatever all trials were combined or only adjuvant chemotherapy studies were considered. The overall meta-analysis showed that the hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour of the addition of induction chemotherapy to a standard surgical procedure and 0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95% CI 0.83-0.94). It was not statistically significant in stage III although the trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69-1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in stages I and II resected NSCLC. More data are needed to confirm such a role for induction chemotherapy. Further trials should separate stage III disease from earlier stages.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

A phase II study evaluating the cisplatin and epirubicin combination in patients with unresectable malignant pleural mesothelioma.

Few chemotherapeutic agents have demonstrated their efficacy in malignant mesothelioma. The cisplatin plus doxorubicin combination has one of the highest response rates. Epirubicin is an anthracyclin, analogous to doxorubicin, with a different toxicologic pattern. As there are no data on the activity of the combination cisplatin plus epirubicin in malignant mesothelioma, the European Lung Cancer Working Party (ELCWP) designed a phase II study with response rate as primary objective. Sixty-nine eligible patients with malignant pleural mesothelioma were centrally registered. The majority of the patients were male (n=59), had a Karnofsky performance status of 80 or more (n=62) and presented with an epithelial histologic subtype (n=43). Median age was 62 years. In nine patients, metastases were documented at the initial work-up, mainly in bone, lung and skin. Three hundred and twenty-four cycles of chemotherapy were administered. The main toxicities were nausea and vomiting, neutropenia and alopecia. Among 63 assessable patients, response rate was 19.0% (95% confidence interval [CI] 9-29%). Median survival was 13.3 months. In multivariate analysis, poor prognostic factors for survival were neutrophil count and CALGB groups 4-6. In conclusion, cisplatin plus epirubicin appears as an effective regimen in malignant mesothelioma, with a favourable toxicity profile. However, it does not demonstrate superior activity to other active regimens in this disease.

Adult↗

PubMed2005

[Prognostic factors in lung cancer].

INTRODUCTION: Knowledge of prognostic factors is important for therapeutic decision making but above all, at a population level, for the interpretation of data in the literature and as a guide to clinical research. To be useful in practice they must be both independent and reproducible. Despite an impressive number of publications few descriptions achieve this standard in lung cancer. BACKGROUND: The TNM classification plays a predominant role in the choice of treatment, in prognosis and as an index of performance. Depending on the population studied (small cell or non-small cell cancer, operable or not) other independent factors, identified in large series, improve the prediction of prognosis: sex, age, loss of weight, LDH, leukocytosis, neutrophilia, haemoglobin, serum calcium, NSE, Cyfra 21-1. VIEWPOINT: The numerous biological factors described should be the object of further investigations but may lead to the assessment of new therapeutic strategies. CONCLUSION: Large multicentre studies are essential before a role may be attributed to an independent prognostic factor and before it may be used as a guide to the management of a patient or to improve our prediction of the progress of a patient or a group of patients.

Humans↗

PubMed2004

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis.

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

Biomarkers, Tumor↗

PubMed2004

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients.

The purpose of this study was to determine the prognostic significance of a high pretreatment serum CYFRA 21-1 level (a cytokeratin 19 fragment) adjusted for the effects of well-known co-variables in non-small-cell lung cancer (NSCLC). This meta-analysis based on individual updated data gathered comprehensive databases from published or unpublished controlled studies dealing with the prognostic effect of serum CYFRA 21-1 level at presentation in NSCLC of any stage (nine institutions, 2063 patients). Multivariate regression was carried out with the Cox model. The proportional hazard assumption for each of the selected variables retained in the final model was originally checked by log minus log plots baseline hazard ratio. The follow-up ranged from 25 to 78 months. A total of 1616 events were recorded. In the multivariate analysis performed at the 1-year end point, a high pretreatment CYFRA 21-1 level was an unfavourable prognostic determinant in all centres except one (Hazard ratio (95% confidence interval): 1.88 (1.64-2.15), P<10(-4)). Other significant variables were stage of the disease, age and performance status. Within the first 18 months, the procedure disclosed a nearly similar hazard ratio for patients having a high pretreatment serum CYFRA 21-1 level (1.62 (1.42-1.86), P<10(-4)). For patients who did not undergo surgery, the hazard ratio during the first year of follow-up was 1.78 (1.54-2.07), P<10(-4). Finally, in the surgically treated population, at the 2-year end point, a high pretreatment CYFRA 21-1 and a locally advanced stage remained unfavourable prognostic determinants. In conclusion CYFRA 21-1 might be regarded as a putative co-variable in analysing NSCLC outcome inasmuch as a high serum level is a significant determinant of poor prognosis whatever the planned treatment.

Aged↗

PubMed2004

Is a specific oncological scoring system better at predicting the prognosis of cancer patients admitted for an acute medical complication in an intensive care unit than general gravity scores?

OBJECTIVE: To evaluate the effectiveness of a specific oncologic scoring system-the ICU Cancer Mortality model (ICM)-in predicting hospital mortality in comparison to two general severity scores-the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Simplified Acute Physiology Score (SAPS II). PATIENTS AND METHODS: All 247 patients admitted for a medical acute complication over an 18-month period in an oncological medical intensive care unit were prospectively registered. Their data, including type of complication, vital status at discharge and cancer characteristics as well as other variables necessary to calculate the three scoring systems were retrospectively assessed. RESULTS: Observed in-hospital mortality was 34%. The predicted in-hospital mortality rate for APACHE II was 32%; SAPS II, 24%; and ICM, 28%. The goodness of fit was inadequate except for the ICM score. Comparison of the area under the ROC curves revealed a better fit for ICM (area 0.79). The maximum correct classification rate was 72% for APACHE II, 74% for SAPS II and 77% for ICM. APACHE II and SAPS II were better at predicting outcome for survivors to hospital discharge, although ICM was better for non-survivors. Two variables were independently predicting the risk of death during hospitalisation: ICM (OR=2.31) and SAPS II (OR=1.05). CONCLUSIONS: Gravity scores were the single independent predictors for hospital mortality, and ICM was equivalent to APACHE II and SAPS II.

APACHE↗

PubMed2004

A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear. PATIENTS AND METHODS: We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC). RESULTS: Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups. CONCLUSION: The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.

Administration, Oral↗

PubMed2004

Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma.

OBJECTIVES: Topoisomerase II-alpha (T2a) is being actively investigated as a potential predictive marker of response to anthracyclines in breast cancer (BC). Although the role of T2a inhibitors as upfront and salvage treatment for epithelial ovarian carcinoma (EOC) remains unclear, we speculated that a small subgroup of ovarian cancer patients could derive a selective benefit from these agents. In this study, we investigated the actual rates of T2a and HER-2 amplification and overexpression by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. METHODS: Seventy-three samples of chemotherapy-naive patients with EOC were selected from our archives. FIGO stage and histology were available for most patients. RESULTS: Based on arbitrary cut-offs of > or =1.5 and > or =2 (ratio copies/centromere17), amplification rates for HER-2 were 15/64 (23.4%) and 8/64 (12.5%) versus 16/64 (25%) and 5/64 (7.8%) for T2a. We found only 3/72 (4.2%) cases of HER-2 overexpression (3+) versus 15/70 (21.4%) for T2a (staining of >10% of the cells). There was a modest correlation between T2a amplification and overexpression (P=0.01) and a strong correlation between T2a and HER-2 amplification when these markers were analysed as continuous variables (P<0.001). T2a amplification significantly correlated with advanced FIGO stage (P=0.02). CONCLUSION: The assessment of HER-2 and T2a amplification and overexpression by FISH and IHC, respectively, is feasible in EOC. These tests can be used for large-scale evaluation of the potential predictive and prognostic value of these markers in the future. Further studies with a special focus on T2a are needed to determine the best cut-offs for potential clinical use in the future.

Antigens, Neoplasm↗

PubMed2004

HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.

Adolescent↗

PubMed2004

A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer.

PURPOSE: The aim of this study was to determine the role of chemotherapy dose intensity in patients with initially unresectable non-metastatic non-small-cell lung cancer (NSCLC), with survival as primary end point, by testing two different regimens as induction chemotherapy followed by thoracic irradiation. PATIENTS AND METHODS: Patients had pathologically proven NSCLC, an initially unresectable non-metastatic tumour without homolateral malignant pleural effusion, no prior history of malignancy and had received no prior therapy. Treatment was randomised for chemotherapy between three courses of MIP (mitomycin C 6 mg/m2; ifosfamide 3 g/m2; cisplatin 50 mg/m2) or SuperMIP (mitomycin C 6 mg/m2; ifosfamide 4.5 g/m2; cisplatin 60 mg/m2, carboplatine 200 mg/m2), followed by chest irradiation (60 Gy; five times per week, for 6 weeks). If the tumour became resectable after chemotherapy, surgery was performed, followed by mediastinal irradiation. RESULTS: A total of 351 patients were eligible: 176 in the MIP arm and 175 in the SuperMIP arm, with 43% and 51% stages IIIA and IIIB, respectively. There was a significantly higher objective response rate with SuperMIP (46%) compared with MIP (35%) (P=0.03) [95% confidence interval (CI) for the difference between the response rates, 1% to 22%]. After induction chemotherapy, surgery was performed in 54 (15%) patients (27 per arm) and chest irradiation in 203 (57%) patients (102 in the MIP arm and 101 in the SuperMIP). In terms of survival, there was no statistically significant difference between the two study arms (P=0.16), with median survival times of, for MIP and SuperMIP, respectively, 12.5 (95% CI 10.1-14.9) and 11.2 (95% CI 9.7-12.8) months. Haematological toxicity and dosage reductions were higher with SuperMIP, which was nevertheless associated with a significantly increased absolute dose intensity. CONCLUSIONS: High dose-intensity induction chemotherapy does not improve survival in initially unresectable non metastatic NSCLC.

Adult↗

PubMed2004

Correlation between topoisomerase-IIalpha gene amplification and protein expression in HER-2 amplified breast cancer.

Topoisomerase-IIalpha (topo-II) is a molecular target for topo-II inhibitors, which makes it a potential predictive marker of responsiveness to these agents. We aim to correlate topo-II gene and protein status on 103 HER-2 amplified breast cancer samples. Paraffin-embedded blocks were screened by FISH for topo-II gene amplification (topo-II: CEP17 ratio >/=1.5; triple probe by Vysis inc.) and analyzed by IHC for topo-II protein expression (continuous variable; clone KiS1) and Ki-67 (positive if >25% of stained cells; clone MIB-1). Topo-II gene amplification was observed in 36.9% (38/103) of the HER-2 amplified study population. HER-2 amplification level (e.g. copy number) was not shown to be predictive for topo-II amplification. The median percentage of topo-II positively stained cells by IHC for topo-II non-amplified and amplified cases were 5% and 10%, respectively. A weak but significant correlation was observed between topo-II gene amplification level and percentage of positively stained cells (Spearman's ranks correlation coefficient of 0.23, p=0.02), the observed correlation being higher in patients with positive staining for Ki-67. Contrary to HER-2, where gene amplification is almost always correlated with protein overexpression in breast cancer, topo-II gene amplification apparently does not always lead to protein overexpression, at least when the latter is evaluated by IHC. Other factors, specifically the tumor proliferation status, may interfere with the topo-II protein status. Although the great majority of topo-II gene aberrations occur in HER-2 positive tumors, the level of HER-2 amplification does not predict for topo-II amplification.

Antigens, Neoplasm↗