Derek S. Tsang

Photophysical, electrochemical, and crystallographic investigation of conjugated fluoreno azomethines and their precursors

The photophysical investigation of amino- and aldehyde-substituted fluorenes revealed that these compounds are not only highly fluorescent, but dissipation of their singlet excited energy occurs by a combination of nonradiative means involving intersystem crossing (ISC) and internal conversion (IC). Quantification of the triplet state formed by ISC was possible by laser-flash photolysis (LFP). The efficiency by which this manifold was populated varied between 10 and 40% depending on the fluorene substitution. Condensation of these aldehyde and amine precursors yielded conjugated thiopheno azomethines with robust covalent bonds. Fluorescence of the azomethinefluorene derivatives was reduced relative to their precursors while the degree of IC remained unchanged. Deactivation of the singlet excited state occurred predominately by ISC and the resulting triplet state was rapidly and efficiently quenched by energy transfer by the azomethine linkage. Cyclic voltammetry of the fluoreno azomethines showed both oxidation and reduction processes, and the measured redox potentials and the band-gaps are lower than a bisfluorene analogue. The fluoreno azomethine LUMO energy levels are sufficiently low, making them compatible with common cathodes, therefore eliminating the use of an electron-injection layer.

Survival outcomes in elderly patients with glioblastoma.

AIMS Many elderly glioblastoma patients are excluded from randomised trials due to age, comorbidity or poor functional status. The purpose of this study was to describe the survival outcomes in all elderly patients with glioblastoma managed at a tertiary cancer centre. MATERIALS AND METHODS A retrospective chart review identified 235 elderly patients (age 65 years or over) with a histological diagnosis of glioblastoma between 1 December 2006 and 31 December 2013. The primary outcome of this study was overall survival by treatment type. Univariate and multivariate Cox proportional hazard models were used to explore significant prognostic variables associated with overall survival. RESULTS The median survival for all patients was 6.5 months (95% confidence interval 5.3-7.7), with 1 year overall survival of 23.7% (95% confidence interval 18.8-30.0). The median survival for patients treated with radiation and chemotherapy was 11.1 months (95% confidence interval 8.1-13.7). Patients treated with radiation alone had a median survival of 6.8 months (95% confidence interval 5.6-7.9). For patients managed with comfort measures only, the median survival was 1.9 months (95% confidence interval 1.6-2.6). Univariate analysis revealed age, performance status, surgery type (biopsy, subtotal resection, gross total resection) and type of treatment received (comfort measures only, radiotherapy alone, radiotherapy and chemotherapy) to be statistically associated with overall survival. In the multivariate analysis, only two predictive factors (treatment received and surgery type) were significant. CONCLUSIONS Elderly patients with glioblastoma selected for treatment (surgery followed by radiation alone or radiation and chemotherapy) survive longer than patients managed with comfort measures. Prospective randomised trials will help guide management for patients eligible for therapy. Elderly patients with glioblastoma who are deemed not eligible for active therapy have very short survival.

Increasing Compliance With an Antibiotic Prophylaxis Guideline to Prevent Pediatric Surgical Site Infection: Before and After Study.

OBJECTIVES To evaluate an intervention for improving antibiotic prophylaxis (AP) guideline compliance to prevent surgical site infections in children. BACKGROUND Although appropriate AP reduces surgical site infection, and guidelines improve quality of care, changing practice is difficult. To facilitate behavioral change, various barriers need to be addressed. METHODS A multidisciplinary task force at a pediatric hospital developed an evidence-based AP guideline. Subsequently, the guideline was posted in operating rooms and the online formulary, only recommended antibiotics were available in operating rooms, incoming trainees received orientation, antibiotic verification was included in time-out, computerized alerts were set for inappropriate postoperative prophylaxis, and surgeons received e-mails when guideline was not followed. AP indication and administration were documented for surgical procedures in July 2008 (preintervention), September 2011 (postintervention), and April-May 2013 (follow-up). Compliance was defined as complete--appropriate antibiotic, dose, timing, redosing, and duration when prophylaxis was indicated; partial--appropriate drug and timing when prophylaxis was indicated; and appropriate use--complete compliance when prophylaxis was indicated, no antibiotics when not indicated. Compliance at preintervention and follow-up was compared using χ(2) tests. RESULTS AP was indicated in 43.9% (187/426) and 62.0% (124/200) of surgical procedures at preintervention and follow-up, respectively. There were significant improvements in appropriate antibiotic use (51.6%-67.0%; P < 0.001), complete (26.2%-53.2%; P < 0.001) and partial compliance (73.3%-88.7%, P = 0.001), correct dosage (77.5%-90.7%; P = 0.003), timing (83.3%-95.8%; P = 0.001), redosing (62.5%-95.8%, P = 0.003), and duration (47.1%-65.3%; P < 0.002). CONCLUSIONS A multifaceted intervention improved compliance with a pediatric AP guideline.

Spectroscopic studies of a fluorescent fluoresceinophane formed via a practical synthetic route

A practical macrocycle synthesis incorporating a highly fluorescent fluorescein was developed. Photophysical, crystallographic and dynamic-NMR studies showed the alkyl tether forces a constrained conformation of the fluoresceinophane, which enhances the fluorescence quantum yields by reducing the excited-state deactivation pathways. Enhanced temperature-dependent fluorescence relative to its linear analogue was also found as a result of the constrained macrocycle conformation, while a manifold shift from the singlet to the triplet state still occurred in different polar solvents.

Quantifying potential reduction in contrast dose with monoenergetic images synthesized from dual-layer detector spectral CT

OBJECTIVE To estimate the potential dose reduction in iodinated contrast when interpreting monoenergetic images from spectral CT. METHODS 51 paediatric patients received contrast-enhanced CT simulation for radiation therapy using a single-source, dual-layer detector spectral CT. The contrast-to-noise ratios (CNRs) of blood vessels were measured relative to surrounding soft tissue. CNRs on monoenergetic 40-70 keV images were compared with polychromatic 120 kVp images. To compare with in vivo results, a phantom with iodine inserts (2-20 mg ml-1 concentration) was scanned and CNRs were calculated relative to water background. RESULTS Monoenergetic keV and body site had significant effects on CNR ratio (p < 0.0001). Across all body sites, the mean CNR ratio (monoenergetic/polychromatic CNR) was 3.3 (20th percentile [%20] 2.6), 2.4 (%20 2.1), 1.7 (%20 1.5), 1.2 (%20 1.0) for 40, 50, 60 and 70 keV images, respectively. Image noise was highest at 40 keV and lowest at 70 keV. Phantom measurements indicated that the same CNR as 120 kVp images can be achieved with a 4.0-fold lower iodine concentration on 40 keV images and 2.5-fold lower on 50 keV images. CONCLUSION 50 keV monoenergetic images provided the best balance of improved CNR on all studies (mean 2.4-fold increase in vivo) for enhancing vessels vs image noise. A 50% reduction in contrast dose on a 50 keV image should maintain comparable or better CNR as compared with polychromatic CT in over 80% of CT studies. Advances in knowledge: Use of a novel, single-source, dual-layer detector spectral CT scanner to improve visualization of contrast-enhanced blood vessels will reduce the amount of iodinated contrast required for radiation oncology treatment planning.

Bone Health Care for Patients With Prostate Cancer Receiving Androgen Deprivation Therapy

Abstract Patients with prostate cancer often receive androgen deprivation therapy (ADT) as part of their treatment regimen. However, treatment with ADT causes multiple side effects, including reduced bone mineral density (BMD), lower lean body mass, and a higher risk for fractures. Several organizations provide clinical practice guidelines for osteoporosis screening, prevention, and treatment in this population, but adherence to these guidelines remains low. Areas for improvement in provider adherence include baseline and follow-up BMD testing, as well as counseling regarding healthy bone behaviors such as calcium/vitamin D intake, lifestyle changes, and physical exercise. Comparison of osteoporosis care in breast cancer and non-oncology populations shows that suboptimal bone health care is not isolated to prostate cancer. A summary of the literature examining improvements in patient adherence and provider delivery of bone health care is included in this review, but high-quality studies are lacking. Patients may be the most receptive to written educational information delivered at or near the time of ADT initiation. Involvement of a primary care practitioner and oncologist in care delivery is associated with higher BMD test use. Institution-level programs that automatically initiate osteoporosis screening and management may be effective at reducing the incidence of hip fracture. Lastly, suggestions are provided for future approaches to knowledge translation and quality of care studies to improve bone health.

Treatment and outcomes for primary cutaneous extramedullary plasmacytoma: a case series

BACKGROUND Primary cutaneous plasmacytoma (pcp) is a rare disease, with few studies to guide therapy. Our primary study objective was to define treatments used for pcp; a secondary objective was to describe outcomes of patients, including disease recurrence and death. METHODS An institutional cancer registry was used to identify cases for retrospective chart review. In a systematic review, treatments for, and outcomes of, all known cases of pcp were described. RESULTS Three eligible cases identified at our institution; each patient had a solitary pcp. The systematic review identified 66 patients. Radiotherapy was the most commonly used primary treatment modality (31% of all patients; 42% for patients with solitary lesions), followed by surgery (28% of all patients; 36% for patients with solitary lesions). Median survival for all patients was 10.4 years [95% ci: 4.3 years to not reached], with a trend toward a decreased risk of death with solitary lesions compared with multiple lesions (hazard ratio: 0.37; 95% ci: 0.13 to 1.08; p = 0.059). For patients with solitary lesions, the median and recurrence-free survivals were, respectively, 17.0 years (95% ci: 1.7 years to not reached) and 11.0 years (95% ci: 2 years to not reached); for patients with multiple lesions, they were 4.3 years (95% ci: 1.3 to not reached) and 1.4 years (95% ci: 0.6 years to not reached). Disease recurrence, including progression to multiple myeloma, was the most common cause of death. CONCLUSIONS Compared with patients having multiple pcp lesions, those presenting with a single pcp lesion might experience longer overall survival. Local therapy (radiation or surgery) is a reasonable curative treatment for a solitary pcp lesion.

A Randomized Controlled Trial of Lorazepam to Reduce Liver Motion in Patients Receiving Upper Abdominal Radiation Therapy

PURPOSE Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. METHODS AND MATERIALS Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. RESULTS Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. CONCLUSIONS Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.

Hospitalizations in elderly glioblastoma patients

BACKGROUND Elderly glioblastoma (GB) patients are at risk of hospitalizations due to the morbidity of the disease and possible treatment toxicity. METHODS In this observational cohort study, 255 newly diagnosed GB patients age 65 years and older were included. Survival, emergency room visits and admissions to an acute care hospital were determined. Mean and median total health care costs were calculated. Risk factors for Emergency room visits and acute care hospital admissions were determined. RESULTS Median overall survival was 6 months. The majority of patients (68%) had at least one visit to the emergency department and 77% had at least one admission to acute care. The mean and median total costs (hospital, ambulatory, physician billing, other health care costs) per patient were

Poster - 31: Predicting IQ and hearing loss following radiotherapy in pediatric brain tumors: proton vs photon

162,479.78 (CAN) and