Radiation therapy in the last month of life

Aim

We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life.

Background

Few objective data exist for radiation therapy (RT) delivery at end of life (EOL).

Materials and methods

Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life.

Results

A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2–30 days).

Conclusions

Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric.     

Selective control of primer usage in multiplex one-step reverse transcription PCR

Background  

Multiplex RT-PCR is a valuable technique used for pathogen identification, disease detection and relative quantification of gene expression. The simplification of this protocol into a one-step procedure saves time and reagents. However, intensive PCR optimization is often required to overcome competing undesired PCR primer extension during the RT step.     

BOLD Correlates of Trial-by-Trial Reaction Time Variability in Gray and White Matter: A Multi-Study fMRI Analysis

Background

Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks.

Methodology/Principal Findings

The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a “time-on-task” effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter.

Conclusions/Significance

The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal.     

Tafazzin Protein Expression Is Associated with Tumorigenesis and Radiation Response in Rectal Cancer: A Study of Swedish Clinical Trial on Preoperative Radiotherapy

Background

Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT.

Methods

140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins.

Results

TAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063–35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3.

Conclusions

Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.     

Age Differences in Intra-Individual Variability in Simple and Choice Reaction Time: Systematic Review and Meta-Analysis

Background

Intra-individual variability in reaction time (RT IIV) is considered to be an index of central nervous system functioning. Such variability is elevated in neurodegenerative diseases or following traumatic brain injury. It has also been suggested to increase with age in healthy ageing.

Objectives

To investigate and quantify age differences in RT IIV in healthy ageing; to examine the effect of different tasks and procedures; to compare raw and mean-adjusted measures of RT IIV.

Data Sources

Four electronic databases: PsycINFO, Medline, Web of Science and EMBASE, and hand searching of reference lists of relevant studies.

Study Eligibility

English language journal articles, books or book chapters, containing quantitative empirical data on simple and/or choice RT IIV. Samples had to include younger (under 60 years) and older (60 years and above) human adults.

Study Appraisal and Synthesis

Studies were evaluated in terms of sample representativeness and data treatment. Relevant data were extracted, using a specially-designed form, from the published report or obtained directly from the study authors. Age-group differences in raw and RT-mean-adjusted measures of simple and choice RT IIV were quantified using random effects meta-analyses.

Results

Older adults (60+ years) had greater RT IIV than younger (20–39) and middle-aged (40–59) adults. Age effects were larger in choice RT tasks than in simple RT tasks. For all measures of RT IIV, effect sizes were larger for the comparisons between older and younger adults than between older and middle-aged adults, indicating that the age-related increases in RT IIV are not limited to old age. Effect sizes were also larger for raw than for RT-mean-adjusted RT IIV measures.

Conclusions

RT IIV is greater among older adults. Some (but not all) of the age-related increases in RT IIV are accounted for by the increased RT means.     

Real-time three-dimensional transthoracic echocardiography in daily practice: initial experience

Aim of the work

To evaluate the feasibility and possible additional value of transthoracic real-time three-dimensional echocardiography (RT3D-TTE) for the assessment of cardiac structures as compared to 2D-TTE.

Methods

320 patients (mean age 45 ± 8.4 years, 75% males) underwent 2D-TTE and RT3D-TTE using 3DQ-Q lab software for offline analysis. Volume quantification and functional assessment was performed in 90 patients for left ventricle and in 20 patients for right ventricle. Assessment of native (112 patients) and prosthetic (30 patients) valves morphology and functions was performed. RT3D-TTE was performed for evaluation of septal defects in 30 patients and intracardiac masses in 52 patients.

Results

RT3D-TTE assessment of left ventricle was feasible and reproducible in 86% of patients while for right ventricle, it was (55%). RT3D-TTE could define the surface anatomy of mitral valve optimally (100%), while for aortic and tricuspid was (88% and 81% respectively). Valve area could be planimetered in 100% for the mitral and in 80% for the aortic. RT3D-TTE provided a comprehensive anatomical and functional evaluation of prosthetic valves. RT3D-TTE enface visualization of septal defects allowed optimal assessment of shape, size, area and number of defects and evaluated the outcome post device closure. RT3D-TTE allowed looking inside the intracardiac masses through multiple sectioning, valuable anatomical delineation and volume calculation.

Conclusion

Our initial experience showed that the use of RT3D-TTE in the assessment of cardiac patients is feasible and allowed detailed anatomical and functional assessment of many cardiac disorders.     

Eleven fetal echocardiographic planes using 4-dimensional ultrasound with spatio-temporal image correlation (STIC): a logical approach to fetal heart volume analysis

Background

Real time three dimensional (RT3D) echocardiography is an accurate and reproducible method for assessing left ventricular shape and function.

Aim

assess the feasibility and reproducibility of RT3D stress echocardiography (SE) (exercise and pharmacological) in the evaluation of left ventricular function compared to 2D.

Methods and results

One hundred eleven patients with known or suspected coronary artery disease underwent 2D and RT3DSE. The agreement in WMSI, EDV, ESV measurements was made off-line. The feasibility of RT-3DSE was 67%. The inter-observer variability for WMSI by RT3D echo was higher during exercise and with suboptimal quality images (good: k = 0.88; bad: k = 0.69); and with high heart rate both for pharmacological (HR < 100 bpm, k = 0.83; HR ≥ 100 bpm, k = 0.49) and exercise SE (HR < 120 bpm, k = 0.88; HR ≥ 120 bpm, k = 0.78). The RT3D reproducibility was high for ESV volumes (0.3 ± 14 ml; CI 95%: -27 to 27 ml; p = n.s.).

Conclusions

RT3DSE is more vulnerable than 2D due to tachycardia, signal quality, patient decubitus and suboptimal resting image quality, making exercise RT3DSE less attractive than pharmacological stress.     

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

Objective

We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).

Methods

Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events.

Results

Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.

Conclusion

Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.     

Real-Time Three-Dimensional Echocardiography to Assess Right Ventricle Function in Patients with Pulmonary Hypertension

Background

The convenience and availability of real-time three-dimensional echocardiography (RT3DE) makes it an attractive candidate for assessing right ventricle function. However, the viability of RT3DE is not conclusive.

Aim of Study

This study aims to evaluate RT3DE relative to cardiac magnetic resonance and 2-dimensional echocardiography (2DE) for measuring right ventricular systolic function in patients with pulmonary hypertension.

Methods

Patients with pulmonary hypertension (n = 23) underwent cardiac magnetic resonance, 2DE, and RT3DE. Specifically, 2DE was used to measure the right ventricular index of myocardial performance (RIMP), fractional area change, tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler-derived tricuspid annular systolic velocity (S′). Cardiac magnetic resonance and RT3DE were used to measure right ventricular end-diastolic volume (RVEDV) and end-systolic volume (RVESV). The right ventricular ejection fraction (RVEF) was calculated.

Results

Regarding the measurements taken by 2DE, RVEF positively correlated with fractional area change (r = 0.595, P = 0.003) and S′(r = 0.489, P = 0.018), and negatively correlated with RIMP (r = −0.745, P = 0.000). There was no association between RVEF and TAPSE (r = −0.029, P = 0.896). There existed a close correlation between the values of RVEDV, RVESV, and RVEF as measured by RT3DE and CMR respectively (P<0.001); Bland-Altmanan analyses showed good agreement between them.

Conclusion

RT3DE was a viable method for noninvasive, accurate assessment of right ventricular systolic function in patients with pulmonary hypertension.     

Intracellular Persisting Staphylococcus aureus Is the Major Pathogen in Recurrent Tonsillitis

Background

The two major indications for tonsillectomy are recurrent tonsillitis (RT) and peritonsillar abscess (PTA). Unlike PTAs, which are primarily treated surgically, RT is often cured by tonsillectomy only after a series of failed drug therapy attempts. Although the bacteriological background of RT has been studied, the reason for the lack of success of conservative therapeutic approaches is not well understood.

Methods

In a prospective study, tonsil specimens from 130 RT patients and 124 PTA patients were examined for the presence of extra- and intracellular bacteria using antibiotic protection assays. Staphylococcus aureus isolates from RT patients were characterized by pulsed-field gel electrophoresis (PFGE), spa-typing and MSCRAMM-gene-PCR. Their ability for biofilm formation was tested and their cell invasiveness was confirmed by a flow cytometric invasion assay (FACS), fluorescent in situ hybridization (FISH) and immunohistochemistry.

Findings

S. aureus was the predominant species (57.7%) in RT patients, whereas Streptococcus pyogenes was most prevalent (20.2%) in PTA patients. Three different assays (FACS, FISH, antibiotic protection assay) showed that nearly all RT-associated S. aureus strains were located inside tonsillar cells. Correspondingly, the results of the MSCRAMM-gene-PCRs confirmed that 87% of these S. aureus isolates were invasive strains and not mere colonizers. Based upon PFGE analyses of genomic DNA and on spa-gene typing the vast majority of the S. aureus isolates belonged to different clonal lineages.

Conclusions

Our results demonstrate that intracellular residing S. aureus is the most common cause of RT and indicate that S. aureus uses this location to survive the effects of antibiotics and the host immune response. A German translation of the Abstract is provided as supplementary material (Abstract S1).     

Salvage Radiotherapy after Radical Prostatectomy: Prediction of Biochemical Outcomes

Introduction

A significant proportion of patients undergoing salvage radiotherapy (RT) for biochemical recurrence (BCR) following radical prostatectomy (RP) may again experience BCR after salvage RT. Thus, we evaluated the clinical significances of different parameters on the biochemical outcome of RT in salvage setting.

Methods

We reviewed the records of 212 patients who underwent salvage RT between November 2003 and December 2012 for BCR following primary RP. BCR-free survivals after salvage RT were estimated using the Kaplan–Meier method. Cox proportional hazard regression models were used to evaluate the impacts of clinicopathologic parameters on BCR following salvage RT.

Results

The overall median follow-up duration was 63.5 months. The BCR-free survival rate after salvage RT was 58.2% at 5 years. Multivariate analysis showed that a pre-RT prostate-specific antigen (PSA) level of ≤0.5 ng/mL, a pre-RT PSA doubling time (PSADT) of >4.5 months, concomitant androgen deprivation therapy (ADT) with salvage RT, and a positive surgical margin were independent predictors of favorable biochemical outcomes after salvage RT (hazard ratios [HR] = 3.012, 1.132, 2.000, and 1.805, respectively, p = less than 0.001, 0.013, 0.005, and 0.036, respectively). In the early (pre-RT PSA ≤0.5 ng/mL) salvage RT setting, concomitant ADT administration was also shown to be significantly associated with higher risk of BCR-free survival following salvage RT (HR = 2.611, p = 0.038).

Conclusion

Lower pre-RT PSA value, longer PSADT before salvage RT, concomitant ADT administration, and a positive surgical margin were significant predictors of favorable biochemical outcomes following salvage RT performed for BCR after primary RP.     

Comparison of Rebound Tonometry,Perkins Applanation Tonometry and Ocular Response Analyser in Mucopolysaccharidosis Patients

Aims

To investigate the feasibility and to compare three devices measuring intraocular pressure (IOP) in mucopolysaccharidosis patients (MPS): iCare rebound tonometer (RT), Perkins applanation tonometer (PAT) and ocular response analyzer (ORA)

Methods

MPS patients who underwent at least two examinations out of: RT, PAT and ORA at the same visit were identified and retrospectively analyzed in this study.

Results

17 patients fulfilled the inclusion criterion. In all 17 patients IOP measurements were performed with RT (34 eyes) and ORA (33 eyes), while PAT measurement was possible in only 12 (24 eyes) patients. The RT, corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOPg) differed relevantly from IOP assessed with PAT. Corneal clouding in MPS patients correlated positively with PAT, RT and IOPg (r = 0.3, 0.5, and 0.5 respectively), but not with IOPcc (r = 0.07). The MPS-related corneal clouding correlated positively with biomechanical corneal parameters assessed with ORA: corneal hysteresis (r = 0.77) and corneal resistance factor (r = 0.77) either.

Conclusions

RT and ORA measurements were tolerated better than applanation tonometry in MPS patients. IOP measurements assessed with RT and ORA differed relevantly from PAT. Corneal-compensated IOP assessed with ORA seems to be less affected by the MPS-related corneal clouding than applanation or rebound tonometry. RT and ORA measurements should be preferred for IOP assessment in patients with MPS.     

Is There a Benefit in Receiving Concurrent Chemoradiotherapy for Elderly Patients with Inoperable Thoracic Esophageal Squamous Cell Carcinoma?

Background and purpose

The benefit of concurrent chemoradiotherapy (CCRT) in elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients.

Methods and materials

Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73).

Results

No treatment-related deaths occurred and no patients experienced any acute grade 4 non-hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS) rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008). Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients ≤ 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years.

Conclusion

Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit.     

Evidence based radiation oncology with existing technology

Aim

To assess the real contribution of modern radiation therapy (RT) technology in the more common tumoral types in Central America, Caribbean and South America.

Background

RT is an essential tool in the management of cancer. RT can be either palliative or of curative intent. In general, for palliative radiotherapy, major technologies are not needed.

Materials and methods

We analyzed the contribution of RT technology based on published evidence for breast, lung, gastric, gallbladder, colorectal, prostate and cervix cancer in terms of disease control, survival or toxicity with especial focus on Latin America.

Results

Findings indicate that three dimensional conformal radiation therapy (3D RT) is the gold standard in most common type of cancer in the studied regions. Prostate cancer is probably the pathology that has more benefits when using new RT technology such as intensity modulated radiation therapy (IMRT) versus 3DRT in terms of toxicity and biochemical progression-free survival.

Conclusions

In light of the changes in technology, the ever-increasing access of developing countries to such technology, and its current coverage in Latin America, any efforts in this area should be aimed at improving the quality of the radiotherapy departments and centers that are already in place.     

Obesity impact on the attentional cost for controlling posture

Background

This study investigated the effects of obesity on attentional resources allocated to postural control in seating and unipedal standing.

Methods

Ten non obese adults (BMI = 22.4±1.3, age = 42.4±15.1) and 10 obese adult patients (BMI = 35.2±2.8, age = 46.2±19.6) maintained postural stability on a force platform in two postural tasks (seated and unipedal). The two postural tasks were performed (1) alone and (2) in a dual-task paradigm in combination with an auditory reaction time task (RT). Performing the RT task together with the postural one was supposed to require some attentional resources that allowed estimating the attentional cost of postural control. 4 trials were performed in each condition for a total of 16 trials.

Findings

(1) Whereas seated non obese and obese patients exhibited similar centre of foot pressure oscillations (CoP), in the unipedal stance only obese patients strongly increased their CoP sway in comparison to controls. (2) Whatever the postural task, the additional RT task did not affect postural stability. (3) Seated, RT did not differ between the two groups. (4) RT strongly increased between the two postural conditions in the obese patients only, suggesting that body schema and the use of internal models was altered with obesity.

Interpretation

Obese patients needed more attentional resources to control postural stability during unipedal stance than non obese participants. This was not the case in a more simple posture such as seating. To reduce the risk of fall as indicated by the critical values of CoP displacement, obese patients must dedicate a strong large part of their attentional resources to postural control, to the detriment of non-postural events. Obese patients were not able to easily perform multitasking as healthy adults do, reflecting weakened psycho-motor abilities.     

Quality of Life after Post-Prostatectomy Intensity Modulated Radiation Therapy: Pelvic Nodal Irradiation Is Not Associated with Worse Bladder,Bowel, or Sexual Outcomes

Background

Limited data exist regarding toxicity and quality of life (QOL) after post-prostatectomy intensity modulated radiation therapy (IMRT) and whether pelvic nodal RT influences these outcomes.

Methods

118 men were treated with curative-intent RT after radical prostatectomy. 69 men (58%) received pelvic nodal RT. QOL data and physician-assigned toxicity were prospectively collected. Changes in QOL from baseline were assessed with Wilcoxon signed-rank tests and risk factors associated with each domain were identified with generalized estimating equation (GEE) models. Late freedom from (FF) toxicity was estimated by the Kaplan-Meier method and comparisons were tested using the log-rank test.

Results

Urinary irritation/obstruction, bowel, and sexual domain scores declined at 2 months (all P ≤ 0.01) but were no different than baseline at subsequent visits through 4 years of follow-up. At 4 years, FF grade 2+ GI toxicity was 90% and FF grade 2+ GU toxicity was 89%. On GEE analysis, pelvic nodal RT was associated with decreased bowel function (P = 0.09) and sexual function (P = 0.01). On multivariate analysis, however, there was no significant association with either decreased bowel (P = 0.31) or sexual (P = 0.84) function. There was also no association with either FF grade 2+ GI toxicity (P = 0.24) or grade 2+ GU toxicity (P = 0.51).

Conclusions

Receipt of pelvic nodal RT was not associated with inferior QOL or toxicity compared to prostate bed alone RT. For the entire cohort, RT was associated with only temporary declines in patient-reported urinary, bowel, or sexual QOL.     

A combined in vitro / in vivo selection for polymerases with novel promoter specificities

Background  

The DNA-dependent RNA polymerase from T7 bacteriophage (T7 RNAP) has been extensively characterized, and like other phage RNA polymerases it is highly specific for its promoter. A combined in vitro / in vivo selection method has been developed for the evolution of T7 RNA polymerases with altered promoter specificities. Large (10³ – 10⁶) polymerase libraries were made and cloned downstream of variant promoters. Those polymerase variants that can recognize variant promoters self-amplify both themselves and their attendent mRNAs in vivo. Following RT / PCR amplification in vitro, the most numerous polymerase genes are preferentially cloned and carried into subsequent rounds of selection.