Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation.

BACKGROUND: Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. METHODS: Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. RESULTS: A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. CONCLUSION: Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Vertebral fractures in multiple myeloma: first results of assessment of fracture risk using dynamic contrast-enhanced magnetic resonance imaging.

The objective of this study was to evaluate dynamic contrast-enhanced magnetic resonance imaging (d-MRI) as a prognostic indicator of lumbar vertebral fractures in patients with multiple myeloma. d-MRI of the lumbar spine was performed in ten patients with multiple myeloma. A fast gradient echo sequence (turbo fast low-angle shot, two-dimensional) was used, together with controlled bolus injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The maximum increase in signal intensity [amplitude (A),arbitrary units (a.u.)] was assessed for each lumbar vertebra. About half a year later (median: 6.2 months) magnetic resonance imaging was repeated to detect new fractures. Amplitudes of vertebrae which fractured after the initial d-MRI were compared with amplitudes of vertebrae which did not fracture during follow-up. Six of ten patients (7 of 50 lumbar vertebrae) showed new fractures. Five patients fractured one vertebra each, whereas one patient had several vertebrae involved. The initial d-MRI showed significantly higher amplitudes (p<0.0001) in those vertebrae that subsequently fractured (A: 33.1+/-8.1 vs 16.7+/-4.2). On retrospective analysis, a cutoff level of 25 a.u. discriminated without overlap between vertebrae that fractured during follow-up and those which did not. The maximum increase in signal intensity (the amplitude) on d-MRI appears to be a prognostic marker capable of predicting vertebral fractures of the lumbar spine in patients with multiple myeloma. d-MRI may therefore be helpful in identifying patients who might benefit from localized radiation therapy or surgical intervention.

Assessment of the value of MR imaging for examining patients with angiographically negative subarachnoid hemorrhage.

OBJECTIVE: Our goal was to assess the value of MR imaging to patient care in the setting of angiographically negative subarachnoid hemorrhage and to evaluate the potential of MR imaging for revealing the mechanism for idiopathic perimesencephalic subarachnoid hemorrhage. MATERIALS AND METHODS: We retrospectively reviewed 71 patients who presented with subarachnoid hemorrhage and in whom the results of a four-vessel cerebral arteriogram were negative, a CT scan showed no evidence of intraaxial hemorrhage, and MR imaging had been performed within 72 hr of presentation. MR imaging of the brain included sagittal spin-echo T1-weighted, turbo spin-echo proton density-weighted, T2-weighted, and axial T2-weighted gradient-echo sequences. MR imaging of the cervical spine, which was performed in 41 of the 71 patients, included sagittal spin-echo T1-weighted, turbo spin-echo proton density-weighted, T2-weighted, and axial T2-weighted gradient-echo sequences. RESULTS: Perimesencephalic subarachnoid hemorrhage was seen on CT in 25 patients; in four of these patients (16%), MR imaging revealed acute perforator territory infarction involving the caudate, putamen, or thalamus. In 26 other patients, nonperimesencephalic subarachnoid hemorrhage was revealed on CT; in two of these patients (8%), MR imaging showed the cause of the subarachnoid hemorrhage. By contrast, 20 patients had negative findings on CT scans but xanthochromic CSF on lumbar puncture; in two of these patients (10%), MR findings were interpreted as responsible for subarachnoid hemorrhage. CONCLUSION: MR imaging showed diagnostic value in patients with angiographically negative subarachnoid hemorrhage, revealing abnormalities in 14% of the 71 patients, and resulted in a significant change in patient treatment in 6% of the patients. MR imaging also revealed an association between perimesencephalic subarachnoid hemorrhage and infarcts involving the territory of perforating arteries at the base of the brain. This finding may provide insight into the pathogenesis of perimesencephalic subarachnoid hemorrhage.

Marketing factors affecting physician choice as related to consumers' extent of use and predisposition toward use of physician services.

This study explores the relationship between predisposition toward, and the extent of actual use of, physician services. Factors in a physician's marketing offering of most importance to consumers in various predisposition and use categories are identified along with their demographic differences, and marketing strategy implications are noted.

Microscope densitometer system for point measurement of autoradiograms.

A photometric system for measuring optical densities generated by tissue autoradiograms has been adapted to an ordinary light microscope. The optics of the microscope are used to direct the light transmitted through the autoradiogram to ocular-mounted photoconductive cells coupled to a bridge amplifier. Readout is on a digital panel meter. The integrated area analyzed varies between 33.16 to 0.02 0.02 mm2 depending on the objective magnification. The system is linear over a range of optical densities from 0.5 to 0.05.