Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: satellite--a phase II study from the Swedish Lung Cancer Study Group.

BACKGROUND: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. METHODS: Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1>1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². TOXICITY was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. RESULTS: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. HISTOLOGY: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss>5%. TOXICITY: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. CONCLUSION: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. TOXICITY, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.

Characterization of indoor sources of fine and ultrafine particles: a study conducted in a full-scale chamber.

UNLABELLED: Humans and their activities are known to generate considerable amounts of particulate matter indoors. Some of the activities are cooking, smoking and cleaning. In this study 13 different particle sources were for the first time examined in a 32 m3 full-scale chamber with an air change rate of 1.7 +/- 0.1/h. Two different instruments, a condensation particle counter (CPC) and an optical particle counter (OPC) were used to quantitatively determine ultrafine and fine particle emissions, respectively. The CPC measures particles from 0.02 microm to larger than 1.0 microm. The OPC was adjusted to measure particle concentrations in eight fractions between 0.3 and 1.0 microm. The sources were cigarette side-stream smoke, pure wax candles, scented candles, a vacuum cleaner, an air-freshener spray, a flat iron (with and without steam) on a cotton sheet, electric radiators, an electric stove, a gas stove, and frying meat. The cigarette burning, frying meat, air freshener spray and gas stove showed a particle size distribution that changed over time towards larger particles. In most of the experiments the maximum concentration was reached within a few minutes. Typically, the increase of the particle concentration immediately after activation of the source was more rapid than the decay of the concentration observed after deactivation of the source. The highest observed concentration of ultrafine particles was approximately 241,000 particles/cm3 and originated from the combustion of pure wax candles. The weakest generation of ultrafine particles (1.17 x 10(7) particles per second) was observed when ironing without steam on a cotton sheet, which resulted in a concentration of 550 particles/cm3 in the chamber air. The highest generation rate (1.47 x 10(10) particles per second) was observed in the radiator test. PRACTICAL IMPLICATIONS: Humans and their activities are known to generate substantial amounts of particulate matter indoors and potentially they can have a strong influence on short-term exposure. In this study a quantitative determination of the emissions of fine and ultrafine particles from different indoor sources was performed. The aim is a better understanding of the origin and fate of indoor particles. The results may be useful for Indoor Air Quality models.

Comparison of three small chamber test methods for the measurement of VOC emission rates from paint.

The aim of this study was to demonstrate a correlation between the measurement of emission rates of volatile organic compounds (VOCs) in three different climate chambers. In order to achieve this aim, the early state of the emission process in the three chambers was investigated and the effects of some important factors on the emission rates from paint were determined. The paper presents results of measurements in three different climate chambers. For the study, a 1-m3 chamber, a field and laboratory emission cell (FLEC), and a chamber for laboratory investigation of materials pollution and air quality (CLIMPAQ) were used. The airflow and surface area were selected so that the area-specific ventilation rates were identical in the three chambers. Temperature and relative humidity were identical during all the measurements. The paint examined was a solvent-based alkyd paint intended for indoor, which use contained between 30 and 60% of white spirit in wet condition. The paint was applied to electropolished and cleaned stainless steel plates. After application, the test material was stored for 14 days for drying in a well-ventilated conditioning room before the measurements were made. After 2 weeks storage, the most pronounced emissions were pentanal, hexanal, octanal, and decanol. The period before the emission rate stabilized differed for the three chambers studied. However, all chambers gave similar emission rates within the overall uncertainty used in these experiments.

Required response time for variable air volume fume hood controllers.

This paper describes results from tests made with the aim of investigating how quickly the exhaust air flow rate through fume hoods needs to be controlled in order to prevent contaminants from leaking out of the fume hood and putting the safety of the laboratory personnel at risk. The measurements were made on a laboratory fume hood in a chemical laboratory. There were no other fume hoods in the laboratory, and the measurements were made without interference from persons entering or leaving the laboratory or walking about in it. A tracer gas method was used with the concentration of dinitrogen oxide (N(2)O) being recorded by a Foxboro Miran 101 infra-red gas analyser. In parallel with the tracer gas measurements, the air velocity through the face opening was also measured, as was the control signal to the damper controlling the air flow rate. The measurements show an increased outward leakage of tracer gas from the fume hood if the air flow rate is not re-established within 1-2 s after the sash is opened. If the delay exceeds 3 s the safety function is temporarily defeated. The measurements were made under virtually ideal conditions. Under more typical conditions, the fume hood could be exposed to various other external perturbations, which means that the control system should re-establish the correct exhaust flow more quickly than indicated by the measurement results obtained under these almost ideal conditions.

What margins should be added to the clinical target volume in radiotherapy treatment planning for lung cancer?

BACKGROUND: The planning target volume in radiotherapy treatment planning takes into account both movements of the clinical target volume (CTV) and set-up deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy for lung cancer were studied. In order to measure the CTV movements due to respiration and other internal organ motions, fluoroscopy was performed for 20 patients. To study the accuracy and reproducibility of patient and beam set-up, 553 electronic portal images from 20 patients were evaluated. Discrepancies between planned and actual field positions were measured and the systematic and random errors were identified. The combined effect of these geometrical variations was evaluated. RESULTS: The average CTV movement with quiet respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions. Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0-12 mm. The systematic set-up errors were on average 2.0 mm in the transversal plane and 3.0 mm in the cranio-caudal direction. The random errors can be described by their standard deviations of 3.2 and 2.6 mm. In this study, the combined effect of the two parameters (CTV movement and set-up deviations) varied between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our daily clinical routine, we use a margin of 11 mm in the transversal plane and 15 mm cranially and caudally, also taking into account other unquantified variations and uncertainties.

Ifosfamide, doxorubicin, vincristine, and etoposide in small cell lung cancer.

From 1982 to 1989, the cyclophosphamide/doxorubicin/vincristine/etoposide combination was the standard treatment for small cell lung cancer in our center. Radiotherapy was started after three cycles, since little further response to chemotherapy could be expected. In 1989, ifosfamide replaced cyclophosphamide, and preliminary results from a pilot study showed impressive early responses. By December 1993, 36 patients had been evaluated, 20 of whom had limited disease and 16 of whom had extensive disease. The response rate was 81% after one cycle and 86% after the second cycle. Median survival time in patients with limited disease was 12 months; in those with extensive disease, it was 7.5 months. Five patients with limited disease are alive and fully active, with an observation time ranging from 29 to 58 months. Based on these findings, our standard treatment protocol has been revised to institute radiotherapy after two cycles of chemotherapy.