Phase II study of ACNU in non-small-cell lung cancer: EORTC study 08872

A total of 62 patients with metastatic or locally advanced non-small-cell lung cancer were entered in a phase II study of ACNU. Initially, the drug was given i. v. at a dose of 100 mg/m2 every 6 weeks, but due to observed haematological side effects in chemotherapy-pretreated patients, the dose was lowered in this group to 75 mg/m2. We observed one complete response in a subject exhibiting multiple lung metastases and a partial response in two patients, one showing brain metastases and one who experienced local disease recurrence. The toxicity of ACNU mainly consisted of bone marrow suppression especially thrombocytopenia, with one toxic death occurring due to intracerebral haemorrhage. We concluded that at this dose and on this schedule, ACNU has limited activity in non-small-cell lung cancer

Can an online clinical data management service help in improving data collection and data quality in a developing country setting?

Background: Data collection by Electronic Medical Record (EMR) systems have been proven to be helpful in data collection for scientific research and in improving healthcare. For a multi-centre trial in Indonesia and the Netherlands a web based system was selected to enable all participating centres to easily access data. This study assesses whether the introduction of a Clinical Trial Data Management service (CTDMS) composed of electronic Case Report Forms (eCRF) can result in effective data collection and treatment monitoring. Methods: Data items entered were checked for inconsistencies automatically when submitted online. The data were divided into primary and secondary data items. We analysed both the total number of errors and the change in error rate, for both Primary and Secondary items, over the first five month of the trial. Results: In the first five months 51 patients were entered. The Primary data error rate was 1.6%, whilst that for Secondary data was 2.7% against acceptable error rates for analysis of 1% and 2.5% respectively. Conclusion: The presented analysis shows that after five months since the introduction of the CTDMS the Primary and Secondary data error rates reflect acceptable levels of data quality. Furthermore, these error rates were decreasing over time. The digital nature of the CTDMS, as well as the online availability of that data, gives fast and easy insight in adherence to treatment protocols. As such, the CTDMS can serve as a tool to train and educate medical doctors and can improve treatment protocols.Maarten A Wildeman, Jeroen Zandbergen, Andrew Vincent, Camelia Herdini, Jaap M Middeldorp, Renske Fles, Otilia Dalesio, Emile van der Donk, I Bing Ta

Diffuse large B-cell non-Hodgkin lymphomas: the clinical relevance of histological subclassification

In the REAL classification the diffuse large B-cell non-Hodgkin lymphomas (NHL) are grouped together, because subclassifications are considered to lack both reproducibility and clinical significance. Others, however, claim that patients with an immunoblastic NHL have a worse prognosis than patients with other types of diffuse large B-cell NHL. Therefore, we investigated the prognostic and clinical significance of histological subclassification of diffuse large B-cell NHL in a uniformly treated series of patients. For this retrospective study, all patients diagnosed as having an immunoblastic (IB) B-cell NHL by the Lymphoma Review Panel of the Comprehensive Cancer Center Amsterdam (CCCA) between 1984 and 1994, and treated according to the guidelines of the CCCA, were analysed. Patients with a centroblastic polymorphic subtype (CB-Poly) or centroblastic (CB) NHL by the Lymphoma Review Panel who were treated in the Netherlands Cancer Institute during the same period according to CCCA guidelines were used as reference groups. All patients' records were reviewed. Clinical parameters at presentation, kind of therapy and clinical outcome were recorded. All available histological slides were separately reviewed by two haemato-pathologists. One hundred and seventy-seven patients were included in the study: 36 patients (20.3%) with an IB NHL, 69 patients (39%) with a CB-Poly NHL and 72 patients (40.7%) with a CB NHL. The patients with an IB NHL tended to be older and presented more often with stage I or II and one extranodal site than patients with a CB and CB-Poly NHL. None of the subtypes showed a clear preference for localization in a particular site. The patients with IB or CB-Poly NHL showed a significantly worse prognosis than patients with CB NHL, with a 5-year overall survival for patients with CB NHL of 56.3% and for patients with IB or CB-Poly NHL 39.1% and 41.6% respectively. The 5-year disease free survival was 53.2% for the patients with CB, 32% for the patients with CB-Poly and 26.9% for the patients with IB NHL. A multivariate analysis showed that histological subtyping was of prognostic significance independent of the International Prognostic Index. This finding merits further exploration in prospective studies in order to judge the value of subclassification of large B-cell NHL as a guideline in therapy choice. © 1999 Cancer Research Campaig

NSLS-II Beam Diagnostics Overview

A new 3rd generation light source (NSLS-II) is in the early stages of construction at Brookhaven National Laboratory. The NSLS-II facility will provide ultra high brightness and flux with exceptional beam stability. It presents several challenges for diagnostics and instrumentation, related to the extremely small emittance. In this paper, we present an overview of all planned instrumentation systems, results from research and development activities; and then focus on other challenging aspects

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy