Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose–volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7–31.2% depending on the /ß ratio of prostate cancer (p

COGNITIVE ASSESSMENT USING THE KINARM EXOSKELETON ROBOT IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACK

Background: Transient ischemic attack (TIA) is a condition causing focal neurological deficits lasting less than 24hrs. TIA patients present similarly to other conditions with rapid onset of neurological symptoms such as migraine. The accurate diagnosis of TIA is critical because it serves as a warning for subsequent stroke. Furthermore, cognitive deficit associated with TIA may predict the development of dementia. Therefore, characterizing the cognitive symptoms of TIA patients and discriminating these patients from those with similar symptoms is important for proper diagnosis and treatment. Currently the diagnosis of TIA is made on clinical and radiographic evidence. Robotic assessment, with instruments such as the KINARM, may improve the identification of cognitive impairment in TIA patients. Methods: In this prospective cohort study, two KINARM tests, trail making task (TMT) and spatial span task (SST), were used to detect cognitive deficits. Two study groups were made. The TIA group was tested at 5 time points over the span of a year. The migraine active control group had one initial visit and another a year later. Both of these groups were compared to a normative database of approximately 400 healthy volunteers. From this database age and sex matched normative data was used to calculate Z-scores for the TMT. The Montreal Cognitive Assessment (MoCA) was also administered to both groups. Results: 31 participants were recruited, 20 TIA group and 11 active controls (mean ± SD age= 66 ± 11.3 and 62 ± 14.5). There was no significant difference in TIA and active control group MoCA scores. The TMT was able to detect cognitive impairment in TIA and migraine group. Also, both KINARM tasks could detect significant differences in performance between TIA and migraine patients while the MoCA could not. Changes in TIA and migraine performance on the MoCA, TMT, and SST were observed. Conclusions: The robotic KINARM exoskeleton can be used to assess cognitive deficits in TIA patients.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.:the results of the LRF AML14 trial

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.