Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.     

The association of endothelial cell signaling,severity of illness,and organ dysfunction in sepsis

Introduction  

Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.     

Dosimetry and field matching for radiotherapy to the breast and supraclavicular fossa

Purpose

Early breast cancer radiotherapy aims for local disease control and reduced recurrence. Treatment is directed to breast or chest wall alone using tangential fields, or includes regional lymph nodes with a separate anterior field. The complex geometry of this region necessitates matching adjacent radiation fields in three-dimensions. Potential exists for overdosage or underdosage and cosmetic results may be compromised if fields are not accurately aligned.

Methods and materials

A study of dosimetry across the match line region using different techniques, as reported in the multicentre START Trial Quality Assurance programme, was undertaken. A custom-made anthropomorphic phantom assessed dose distribution in three-dimensions using film dosimetry.

Results

Methods with varying degrees of complexity were employed for field matching. Techniques combined half beam blocking and machine rotations to achieve geometric alignment. Asymmetric beam matching allowed use of a single isocentre technique. Where field matching was not undertaken a gap between tangential and nodal fields was employed. Results demonstrated differences between techniques and variations for similar techniques in different centres. Geometric alignment techniques produced more homogenous dose distributions in the match region than gap techniques or those techniques not correcting for field divergence.

Conclusions

Field matching techniques during the START trial varied between centres. Film dosimetry used in conjunction with a breast-shaped phantom provided relative dose information. The study highlighted difficulties in matching treatment fields to achieve homogenous dose distribution through the region of the match plane and the degree of inhomogeneity as a consequence of a gap between treatment fields.     

A gyroxin analog from the venom of the bushmaster (Lachesis muta muta)

Clinical observations of possible neurotoxic activity in bushmaster (Lachesis muta muta) envenomations, coupled with the accepted ancestral relationship of Lachesis to other crotalids, suggested that Lachesis venom might contain a crotoxin-like molecule. Crude venom and gel-filtration fractions showed modest reactivity in enzyme-linked immunosorbent assays using rabbit polyclonal antibodies raised against the basic subunit of crotoxin, but no reaction was detected with a murine monoclonal antibody raised against the same antigen. Phospholipase assays, LD50 determinations and SDS-polyacrylamide gel electrophoresis indicated the presence of non-toxic phospholipases, but no crotoxin homologs. A higher mol.wt, toxic protein (60,000) with an LD50 of 0.07 micrograms/g in mice was isolated and purified, which induced gyroxin-like, rapid rolling motions in mice. Its amino terminal sequence shows considerable amino acid sequence identity with gyroxin from the venom of Crotalus durissus terrificus and other serine proteases.     

Inhibitory synaptogenesis in mouse somatosensory cortex

It is widely believed that inhibitory synapses are not present or present in only small numbers in the rodent cerebral cortex during the early postnatal period when the cortex is being innervated by thalamocortical fibers. Quantitative electron microscopy was carried out on the posteromedial barrel subfield of mouse somatosensory cortex from postnatal day 4 (P4) when thalamocortical innervation of the barrels is becoming established, through to sexual maturity (>P32), and in adulthood. Both asymmetrical (putatively excitatory) and symmetrical (putatively inhibitory) synapses were present in all layers from P4. The symmetrical synapses were immunoreactive for GABA at all ages. There was a progressive increase in both asymmetrical and symmetrical synapses up to P32, density in all layers increasing 16-fold, with the production of asymmetrical synapses leading and greatly outstripping that of symmetrical. From P32 to P120, the oldest age studied, synaptic numbers declined by 18% to 13 times the P4 level, but this affected predominantly layers II/III, IV and V, and mainly involved asymmetrical synapses. The relative percentage of asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32 it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that inhibitory synaptogenesis in the rodent cortex begins earlier than previously thought, a basis for inhibition being present from the earliest period. Pruning of all synapses occurs well after thalamocortical innervation is established and inhibitory synapses are less affected by the pruning process.      

The impact of wrist extension provocation on current perception thresholds in patients with carpal tunnel syndrome: a pilot study.

PURPOSE: To determine whether current perception threshold (CPT) varied between subjects with and without carpal tunnel syndrome (CTS) and whether positioning in wrist extension (reversed Phalen's test) was provocative. METHOD: Subjects (n=30) were tested using the Neurometer (Neutron, Inc., Baltimore, MD) at 5, 250, and 2,000 Hz in a rest and reverse Phalen's position. Group and positional differences were analyzed using analysis of variance. RESULTS: Higher CPT occurred at 2,000 Hz in both rest (p=0.02) and reverse Phalen's position (p=0.01) in CTS subjects. There was also a significant change in CPT in the CTS group following wrist extension, particularly at 2,000 Hz (p<0.05). CONCLUSION: A positional effect on sensibility was noted at 2,000 Hz in subjects with CTS. Further evaluation is required to determine the role and optimal test protocols for provocative-sensory testing in diagnosis and outcome assessment of CTS. For CPT these should focus on using the 2,000 Hz frequency.