Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy

This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m2/d, leucovorin 120 mg/m2/d, and cisplatin 20 mg/m2/d for 5 consecutive days. Cycles were repeated at intervals of 5–6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III–IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment. © 2001 Cancer Research Campaign http://www.bjcancer.co

Atto Second Electron Beams Generation and Characterization Experiment at the Accelerator Test Facility.

We are proposing an Atto-second electron beam generation and diagnostics experiment at the Brookhaven Accelerator Test facility (ATF) using 1 {micro}m Inverse Free Electron Laser (IFEL). The proposed experiment will be carried out by an BNL/LBNL collaboration, and it will be installed at the ATF beam line II. The proposed experiment will employ a one-meter long undulator with 1.8 cm period (VISA undulator). The electron beam energy will be 63 MeV with emittance less than 2 mm-mrad and energy spread less than 0.05%. The ATF photocathode injector driving laser will be used for energy modulation by Inverse Free Electron Laser (IFEL). With 10 MW laser peak power, about 2% total energy modulation is expected. The energy modulated electron beam will be further bunched through either a drift space or a three magnet chicane into atto-second electron bunches. The attosecond electron beam bunches will be analyzed using the coherent transition radiation (CTR)

Prediction of outcome in locally advanced breast cancer by post-chemotherapy nodal status and baseline serum tumour markers

In spite of the apparent improvement in outcome in locally advanced breast cancer, the prognosis remains dismal in many patients. The aim of this study was to define prognostic subgroups within this heterogeneous entity. Between 1990 and 1999, 104 consecutive patients with locally advanced breast cancer were treated by a multimodality programme consisting of 4–6 courses of CAF induction chemotherapy followed by surgery, breast-conserving when feasible. In most cases, chemotherapy was then resumed, up to a total of eight courses, followed by locoregional radiation therapy. Patients with hormone receptor-positive tumours received tamoxifen (20 mg day−1) for 5 years. At a median follow-up of 57 months, the 5-year overall survival for the entire group and the disease-free survival for the 94 operated patients were 65% and 53%, respectively. Univariate analysis identified 10 prognostic factors of overall and disease-free survival, of which four retained significance on multivariate analysis: inflammatory breast cancer (P=0.0000, P=0.0004, respectively), baseline tumour markers (P=0.003 for both), post-chemotherapy number of involved nodes (P=0.003; P=0.017) and extracapsular spread (P=0.052; P=0.014). In conclusion, besides inflammatory features, baseline tumour markers and post-chemotherapy nodal status are strong predictors of outcome in locally advanced breast cancer

First Lasing of a High-Gain Harmonic Generation Free-Electron Laser Experiment.

We report on the first lasing of a high-gain harmonic generation (HGHG) free-electron laser (FEL). The experiment was conducted at the Accelerator Test Facility (ATF) at Brookhaven National Laboratory (BNL). This is a BNL experiment in collaboration with the Advanced Photon Source (APS) at Argonne National Laboratory. A preliminary measurement gives a high-gain harmonic generation (HGHG) pulse energy that is 2 x 10{sup 7} times larger than the spontaneous radiation, In a purely self-amplified spontaneous emission (SASE) mode of operation, the signal was measured as 10 times larger than the spontaneous radiation in the same distance ({approximately}2 m) through the same wiggler. This means the HGHG signal is 2 x 10{sup 6} times larger than the SASE signal. To obtain the same saturated output power by the SASE process, the radiator would have to be 3 times longer (6 m)

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups