[Prophylactic cranial irradiation in patients with extensive disease caused by small-cell lung cancer responsive to chemotherapy: fewer symptomatic brain metastases and improved survival]. / Profylactische schedelbestraling bij patiënten met uitgebreid kleincellig longcarcinoom dat reageert op chemotherapie: minder symptomatische hersenmetastasen en betere overleving.

OBJECTIVE: To determine the effect of prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) who responded to chemotherapy. DESIGN: Randomised, controlled clinical trial; phase III study (EORTC nr 08993-22993; www.clinicaltrials.gov, nr NCT00016211). METHOD: Patients aged 18-75 years with a functional status according to WHO < or = 2, and with ED-SCLC and any response to chemotherapy, were randomized to observation (standard care) or PCI. The primary endpoint was time to symptomatic brain metastases. If any pre-defined, key symptom suggesting brain metastases presented, a CT or MRI scan of the brain was performed. The size of the study (143 patients per arm) was determined to detect a hazard ratio (HR) of 0.44 at 80% power with 2-sided alpha = 0.05. RESULTS: The study accrued 286 patients. PCI decreased the risk of developing symptomatic brain metastases (HR = 0.27 (95% CI: 0.16-0.44; p < 0.001)). The cumulative incidence of developing brain metastases within 1 year was 40% in the control group (95% CI: 32-49) and 15% in the PCI group (95% CI: 8-21). PCI prolonged disease-free (HR = 0.76; 95% CI: 0.59-0.96, p = 0.02) and overall survival (HR = 0.68; 95% CI; 0.52-0.88, p = 0.003). The 1-year survival rate was 27% (95% CI: 19-36) for the PCI group versus 13% (95% CI: 8-20) for controls. Acute and late treatment toxicity was acceptable. These side effects did not significantly impact on quality of life. CONCLUSIONS: PCI significantly reduced the incidence of symptomatic brain metastases and prolonged both disease-free and overall survival and should be part of standard care in SCLC patients who respond to chemotherapy.

Influence of age, comorbidity and performance status on the choice of treatment for patients with non-small cell lung cancer; results of a population-based study.

BACKGROUND: In the Netherlands in 1997, 43% of patients with newly diagnosed lung cancer were over 70. Large age-specific differences in treatment exist. We examined whether age, comorbidity, performance status and pulmonary function influenced treatment. PATIENTS AND METHODS: Data on patients with newly diagnosed non-small cell lung cancer (N = 803) were obtained: comorbidity, performance status, pulmonary function (FEV1) and initial treatment. Age-specific differences in treatment according to the guidelines were examined. Odds ratios were calculated by means of logistic regression analyses. RESULTS: 82% with stage I or II disease received treatment according to the guidelines; this applied to 48% with stage IIIA disease and to 54% with stage IIIB disease. For all stages, this proportion decreased with increasing age. In stage IV disease, 36% did not receive any treatment; this applied to 52% of the elderly patients (75+ years). Multivariate analyses showed associations between comorbidity and treatment choice, but none with performance status. Age of 75+ years appeared to be the most important factor for not receiving treatment according to guidelines. CONCLUSION: A substantial proportion of elderly patients with non-small cell lung cancer did not receive standard treatment. Performance status and comorbidity seldom formed the underlying reason. Calendar rather than biological age seemed to play the most important role in choice of treatment for patients with non-small cell lung cancer.

Treatment and survival of patients with non-small cell lung cancer Stage IIIA diagnosed in 1989-1994: a study in the region of the Comprehensive Cancer Centre East, The Netherlands.

The purpose of this study was to gain insight into the treatment policy and survival of patients with non-small cell lung cancer (NSCLC) clinical stage IIIA in daily practice. We selected 212 patients, who had been diagnosed between 1989 and 1994 and registered by the Cancer Registry, Comprehensive Cancer Centre East (CCCE). Diagnostic tests comprised chest X-ray and bronchoscopy in all cases but one, computed tomography in 89%, mediastinoscopy in 55% and conventional tomography of the chest in 16%. NSCLC had been verified histologically in 88% and cytologically in 12%. The initial treatment for the primary tumor had been surgery alone in 13% of the patients, surgery plus radiotherapy in 8%, radiotherapy alone in 56%, chemotherapy in 1% (three patients, one in addition to surgery); 22% received none of these treatments. Median survival of the 212 patients was 9.4 months (95% confidence interval 8.3-11.0 months). Overall survival rates after 1, 2 and 3 years were 41, 17 and 8%, respectively. Three-year survival of the patients who had undergone surgery, surgery plus radiotherapy, radiotherapy alone and no treatment was 18, 19, 6 and 4%, respectively. Treatment was an independent prognostic factor (multivariate Cox's proportional hazards analysis adjusted for sub-stage, age, number of co-morbid diseases and hospital). In the same model, the Hazard rate ratio for one hospital relative to the five others was 1.9 (95% confidence interval 1.2-2.8). Surgery (whether or not in combination with radiotherapy) independently gave the best results. In conclusion, policies varied between hospitals, although the variation in overall survival was small except at one hospital. New regional management guidelines are in preparation. Physicians will be encouraged to follow these guidelines, both with regard to diagnostic tests and to treatment policies, as our study showed that differences in policy might lead to differences in survival.

Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955).

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.

Randomized trial of surgery versus radiotherapy in patients with stage IIIA (N2) non small-cell lung cancer after a response to induction chemotherapy. EORTC 08941.

Combined modality treatment of patients with stage III non small-cell lung cancer (NSCLC) has recently become widely accepted. Standard combinations are neoadjuvant chemotherapy followed by radiotherapy or concurrent chemotherapy and radiotherapy. The effect of combined modality treatment on survival is dependent on both the efficacy of chemotherapy to eradicate micrometastases and optimal local control. The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Cooperative Group has chosen to investigate in a comparative way the side effects and the effect on survival of radiotherapy versus surgery in stage IIIA (N2) NSCLC.

Fabrication of plastic microfluid channels by imprinting methods.

Microfluidic devices have been fabricated on poly(methyl methacrylate) substrates by two independent imprinting techniques. First-generation devices were fabricated using a small-diameter wire to create an impression in plastics softened by low-temperature heating. The resulting devices are limited to only simple linear channel designs but are readily produced at low cost. Second-generation devices with more complex microchannel arrangements were fabricated by imprinting the plastic substrates using an inverse three-dimensional image of the device micromachined on a silicon wafer. This micromachined template may be used repeatedly to generate devices reproducibly. Fluorescent analtyes were used to demonstrate reproducible electrophoretic injections. An immunoassay was also performed in an imprinted device as a demonstration of future applications.

Integrating laboratory robots with analytical instruments--must it really be so difficult?

Creating a reliable system from discrete laboratory instruments is often a task fraught with difficulties. While many modern analytical instruments are marvels of detection and data handling, attempts to create automated analytical systems incorporating such instruments are often frustrated by their human-oriented control structures and their egocentricity. The laboratory robot, while fully susceptible to these problems, extends such compatibility issues to the physical dimensions involving sample interchange, manipulation, and event timing. The workcell concept was conceived to describe the procedure and equipment necessary to carry out a single task during sample preparation. This notion can be extended to organize all operations in an automated system. Each workcell, no matter how complex its local repertoire of functions, must be minimally capable of accepting information (commands, data), returning information on demand (status, results), and being started, stopped, and reset by a higher level device. Even the system controller should have a mode where it can be directed by instructions from a higher level.

A simple, automated device for the precise addition of liquids.

Metering liquid reagents into reaction mixtures in a controlled and reproducible manner has often been a problem in synthetic chemistry. Carrying out the real simultaneous addition of two or more liquid reagents (concurrent additions) is even more inconvenient. Difficulties increase when addition volumes become small, when addition times become long, or when the reagents are corrosive or air-sensitive. We have constructed and tested an inexpensive, automated device for the slow, precise delivery of liquid reagents into laboratory-scale reaction mixtures. Controlled by a standard personal computer, this slow adder can accommodate liquid volumes from hundreds of microlitres to litres and addition times from minutes to days. Its glass and Teflon construction makes it useful for nearly all reagents. By using multiple slow adders, true concurrent addition of several liquids can be easily achieved.

Subcutaneous sacrococcygeal ependymoma with inguinal lymph node metastasis. Case report.

A patient with a subcutaneous sacrococcygeal ependymoma and metastasis to the inguinal lymph nodes is presented and his treatment is described. Previous reports on sacrococcygeal ependymoma are reviewed.