Soluble Triggering Receptor Expressed on Myeloid cells-1 in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia.

PURPOSE: Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) has proven to be a good biomarker for sepsis. For the diagnosis ventilator-associated pneumonia (VAP), however, there have only been a few, relatively small, studies on the role of this receptor. The aim of the study was to evaluate the usefulness of sTREM-1 in bronchoalveolar lavage fluid (BALF) from Intensive Care Unit patients as rapid diagnostic test for VAP. METHODS: The concentration of sTREM-1 in 240 BALF samples was measured using a quantitative sandwich enzyme immunoassay. Two researchers who were blind to the assay results determined whether a VAP was present or not. Clinical suspicion of a VAP was confirmed by the presence of > or = 2% cells containing intracellular organisms and/or a quantitative culture result of > or = 10(4) colony forming units per millilitre BALF. RESULTS: The mean concentration of sTREM-1 was significantly higher in the BALF of patients with confirmed VAP than in that of patients without confirmed VAP. However, the area under the receiver-operating characteristic curve was 0.58 (95% confidence interval 0.50-0.65, P = 0.04). CONCLUSIONS: The results imply that the sTREM-1 assay in BALF may not be discriminative for VAP.

Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI).

BACKGROUND: The aims of this study were to show 1) the effect of changing from computed tomography (CT) to magnetic resonance imaging (MRI) on the prevalence of detected brain metastases (BM) in patients with newly diagnosed small cell lung cancer (SCLC); 2) the difference in survival between patients with single and multiple BM; and 3) the effect of the change in patient labeling on eligibility for prophylactic brain irradiation. METHODS: From 1980 to 2004, 481 consecutive patients with SCLC were enrolled. Brain imaging was routinely performed after diagnosis of SCLC. At the start of 1991, MRI replaced CT in almost all patients. All patients were regularly examined by a neurologist. RESULTS: The prevalence of detected BM was 10% in the CT era and 24% in the MRI era. In the CT era, all detected BM were symptomatic, whereas in the MRI era, 11% were asymptomatic. In both periods, patients labeled as single BM survived longer than those labeled as multiple BM. For patients labeled as single BM or multiple BM, survival was longer in the MRI era than in the CT era. The proportion of patients who were eligible for prophylactic cranial irradiation was lower in the MRI era. CONCLUSIONS: The estimated prevalence of BM increases when MRI is used instead of CT. Patients with a detected single BM survive longer than patients with multiple BM. The apparently increased survival in the MRI era can be attributed to the "Will Rogers phenomenon". The use of MRI makes fewer patients eligible for prophylactic cranial irradiation.

Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial.

PURPOSE: To evaluate the patterns of recurrence when elective node irradiation was omitted in patients with limited disease small cell lung cancer (LD-SCLC). METHODS: A prospective phase II study was undertaken in 27 patients with LD-SCLC without detectable distant metastases on CT scan. Chest radiotherapy to a dose of 45 Gy in 30 fractions in 3 weeks (1.5 Gy BID with 6 - 8 h interval) was delivered concurrently with carboplatin and etoposide chemotherapy. Chest radiation started after a mean time of 17.7 days +/- 9.7 days (SD) (range: 0-33 days) after the beginning of chemotherapy. Only the primary tumour and the positive nodal areas on the pre-treatment CT scan were irradiated. A total of five chemotherapy cycles were administered, followed by prophylactic cranial irradiation (PCI) in patients without disease progression. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. RESULTS: After a median time of 18 months post-radiotherapy, 7 patients (26%, 95% CI 19.5-42.5%) developed a local recurrence. Three patients (crude rate 11%, 95% CI 2.4-29%), developed an isolated nodal failure, all of them in the ipsilateral supraclavicular fossa. The median actuarial overall survival was 21 months (95% CI 15.3-26.7), and the median actuarial progression free survival was 16 months (95% CI 6.5-25.5). Eight patients developed an acute, reversible grade 3 (CTC 3.0) radiation oesophagitis (30%, 95% CI 14-50%). CONCLUSIONS: Because of the small sample size, no definitive conclusions can be drawn. However, the omission of elective nodal irradiation on the basis of CT scans in patients with LD-SCLC resulted in a higher than expected rate of isolated nodal failures in the ipsilateral supraclavicular fossa. The incidence of acute, reversible oesophagitis was in the same range as reported with elective nodal fields. The safety of selective nodal irradiation in NSCLC should not be extrapolated to patients with LD-SCLC until more data are available. In the mean time, elective nodal irradiation should only be omitted in clinical trials.

Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy.

PURPOSE: The purpose of this study was to investigate the radiologic response of asymptomatic brain metastases (BM) from small-cell lung cancer (SCLC) to first-line systemic chemotherapy. PATIENTS AND METHODS: From 1990 to 2003, 181 consecutive patients with SCLC were enrolled onto this study. Patients were examined by a neurologist on a regular basis. Magnetic resonance imaging (MRI) of the brain was performed routinely before (at diagnosis of SCLC) and after first-line systemic chemotherapy. Patients were treated with combination chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Clinically manifest BM were treated with whole-brain radiotherapy (WBRT). The response rate (RR) of BM was assessed by changes in the size or the number of enhanced lesions on MRI using standard criteria. RESULTS: Synchronous asymptomatic BM were found in 24 SCLC patients (13%). In six (27%) of the 22 assessable patients, the asymptomatic BM responded to systemic chemotherapy. A systemic response was found in 16 patients (73%). All patients became symptomatic during follow-up. The symptom-free survival did not differ between cranial responders and cranial nonresponders. CONCLUSION: The RR of asymptomatic BM from SCLC to systemic chemotherapy is 27% and evidently lower than the systemic RR. Future studies should focus on the possible beneficial effect of WBRT for patients with asymptomatic synchronous BM.

Cost-effectiveness of hypothetical new cancer drugs in patients with advanced small-cell lung cancer: results of a markov chain model.

BACKGROUND: In the last decade, a number of new treatment modalities have been developed for patients with small cell lung cancer (SCLC). The clinical effects are encouraging, but little is known about the costs and cost-effectiveness of new drugs. METHODS: A Markov chain model has been developed to project patient outcomes and costs for patients with advanced SCLC. All patients in the control group were treated with etoposide-cisplatin chemotherapy. Patients in the study group received a hypothetical new drug. The model consisted of four states: response, stable disease, progressive disease, and death. Estimates of transition probabilities were calculated using published data on survival and recurrence-free survival. For the cost analysis and utility calculation, published data and expert opinion were used as sources. The duration of the follow-up was maximal 2 years. RESULTS: The total treatment costs in the etoposide-cisplatin group amounted to euro16 038 and in the alternative treatment groups between euro16 644 and euro18 171. The number of life years and quality adjusted life years (QALYs) gained were very small, around 16 days. The cost-effectiveness ratio varied between euro22 208 and euro81 443 and the cost-utility ratio varied accordingly. Results of the sensitivity analysis showed that the results were robust in favor of etoposide-cisplatin treatment. CONCLUSION: SCLC is an illness with a poor prognosis which needed substantial healthcare resources to optimise patient survival and overall quality of life. New treatment modalities with better outcome and favourable cost-effective profiles can hopefully be developed.

Leptomeningeal metastases from small cell lung carcinoma.

BACKGROUND: The current study was performed to investigate the frequency of leptomeningeal metastases (LMM) in patients with small cell lung carcinoma (SCLC) as well as the effect of LMM on survival, any correlation between the location of the LMM and survival, and a possible increased risk of LMM among patients with brain metastases (BM) located in the posterior fossa. METHODS: Between 1980-2003, 458 consecutive patients with SCLC were enrolled in the current study. Patients underwent regular neurologic examination and imaging of the brain before, during, and after treatment. The diagnosis of LMM was established by either the presence of malignant cells in the cerebrospinal fluid or positive clinical symptoms and signs supported by radiologic findings on magnetic resonance imaging. RESULTS: The group of patients in the current study had a 2% prevalence of LMM and the 2-year cumulative incidence of LMM was found to be 10%. The median survival after the diagnosis of LMM was reported to be 1.3 months. The median survival among patients with LMM located in the spinal cord was 2.4 months. The reported LMM-free survival 2 years after the diagnosis of SCLC was 78% for patients without BM and 61% for those patients with BM. Approximately 15% of the patients with BM located in the posterior fossa developed LMM, whereas only 10% of patients with cerebral BM did. CONCLUSIONS: The current prospective study found a 2-year cumulative incidence of LMM of 10%, with a prevalence of 2%. Patients with LMM located in the spinal cord appeared to survive longer than patients with cranial LMM. SCLC patients with BM located in the posterior fossa may be at a higher risk of developing LMM compared with patients with cerebral BM.

Neurologic disorders in 432 consecutive patients with small cell lung carcinoma.

BACKGROUND: Neurologic complications are an important cause of morbidity and possibly also mortality in patients with small cell lung carcinoma (SCLC). The current study was undertaken to prospectively investigate survival and the frequency of neurologic disorders in patients with SCLC. METHODS: Between October 1980 and September 2001, 432 consecutive patients with microscopically proven SCLC were included in the current study. Patients underwent neurologic examinations on a regular basis prior to, during, and after treatment. Routine imaging of the brain (computed tomography or magnetic resonance imaging) was performed before and after systemic therapy. RESULTS: A neurologic disorder was diagnosed in approximately 56% of the SCLC patients. In nearly half of the cases, the neurologic disorder already was present at the time of diagnosis. Brain metastases (BM) were diagnosed most frequently. Seventy-four patients (18%) had BM at the time of diagnosis; in 20 of these patients, the BM did not demonstrate clinical signs. Another 101 patients developed BM during follow-up. The 2-year cumulative risk of BM reached 49% for patients with limited disease (LD) and 65% for patients with extensive disease (ED). Patients with BM as the only site of disease dissemination were found to have a poorer survival compared with LD patients. The majority of the nonmetastatic disorders preceded the diagnosis of SCLC. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed most frequently. CONCLUSIONS: In this prospective study, neurologic disorders were diagnosed in greater than half of the patients with SCLC. BM were detected most frequently. Approximately 18% of the patients were found to have BM at the time of diagnosis. In approximately 33% of the cases, these BM did not cause symptoms. BM were found to have a negative effect on survival in patients with SCLC.

Mediastinal staging of lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography and a dual-head coincidence gamma camera.

The aims of the present study were (a) to evaluate mediastinal staging in patients with lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) using a coincidence gamma camera (hybrid PET) in comparison with dedicated positron emission tomography (PET) and computed tomography (CT), and (b) to assess the feasibility to determine standardized uptake values (SUV) with hybrid PET. Forty patients were included in the study. Hybrid PET was performed without and with attenuation correction. Data were rebinned with single-slice (SSRB) or Fourier rebinning (FORE). The SUVs of primary tumors were calculated with hybrid PET and compared with SUVs determined by dedicated PET. Diagnostic accuracy for hybrid with or without attenuation correction was 80 or 74% compared with 82% for dedicated PET, and 63% for CT. Attenuation-corrected hybrid PET revealed a higher specificity than CT (83 vs 52%; p<0.05). The SUVs of primary tumors were similar to those of hybrid PET and dedicated PET with a mean relative difference of 20.8+/-16.4%. The FORE improved the agreement of SUVs with a mean relative difference of 13.8+/-9.9 vs 36.0+/-17.9% for SSRB ( p<0.001). Hybrid PET with attenuation correction is more specific than CT for mediastinal staging in patients with lung cancer ( p<0.05). It reveals similar results in comparison with dedicated PET. Calculation of SUVs with hybrid PET is feasible.

European organization for research and treatment of cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer.

PURPOSE: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in "sensitive" (s) and "refractory" (r) small-cell lung cancer (SCLC) patients treated previously. EXPERIMENTAL DESIGN: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment <3 months from treatment discontinuation) and s group (patients who responded to first-line treatment and progressed >or=3 months after treatment discontinuation). Cisplatin was given i.v. at the dose of 60 mg/m(2) on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m(2) from day 1 to 5, every 3 weeks. RESULTS: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67% (r) had extensive stage disease, including 22% and 36%, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62% (s) and 49% (r) of patients, with a 19% (s) and 15% (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54% (s) and 44% (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4% response rate; 95% confidence interval, 19-42), whereas, among r patients, 10 partial responses have been observed (23.8% response rate; 95% confidence interval, 12-39). Median survival for s and r was 6.4 and 6.1 months, respectively. CONCLUSIONS: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.

Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer.

PURPOSE: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. PATIENTS AND METHODS: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. RESULTS: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. CONCLUSIONS: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence and severity of radiation-induced changes, and the higher levels of dysphagia persisting up to 12 months, local irradiation of the primary tumor without elective irradiation of the regional lymph nodes may be the most appropriate treatment for patients with small, peripherally located tumors.