Anne Bernard

A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma.

Background Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities. Methods PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I2 test of heterogeneity for multiple studies. Results One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I2=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I2=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I2=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I2=0%). Conclusions We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.

The effect of beam arrangements and the impact of non‐coplanar beams on the treatment planning of stereotactic ablative radiation therapy for early stage lung cancer

The aim of this study was to compare various coplanar and non‐coplanar 3‐dimensional conformal radiation therapy (3DCRT) beam arrangements for the delivery of stereotactic ablative radiation therapy (SABR) to patients with early stage lung cancer, based on the dosimetric criteria from the Radiation Therapy Oncology Group (RTOG) 1021 protocol.

Patient characteristics, interventions and outcomes of 1,151 rapid response team activations in a tertiary hospital: a prospective study

The characteristics of mature contemporary rapid response systems are unclear.

Evaluating the accuracy of the XVI dual registration tool compared with manual soft tissue matching to localise tumour volumes for post‐prostatectomy patients receiving radiotherapy

Cone beam computerised tomography (CBCT) enables soft tissue visualisation to optimise matching in the post‐prostatectomy setting, but is associated with inter‐observer variability. This study assessed the accuracy and consistency of automated soft tissue localisation using XVIs dual registration tool (DRT).

Evaluation of accuracy and reproducibility of a relocatable maxillary fixation system for fractionated intracranial stereotactic radiation therapy

Accurate localisation is an essential component for the delivery of intracranial stereotactic treatment. For fractionated stereotactic radiotherapy, we compared the daily localisation accuracy of a standard thermoplastic mask with a new maxillary fixation device (MFD).

Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer

OBJECTIVES To determine the rate of subsequent primary site failure in patients with head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) in a region with a high prevalence of cutaneous squamous cell carcinoma, according to a pre-determined institutional policy. Secondary aims included regional and distant control, and overall survival. MATERIAL AND METHODS Patients presenting between April 2005 and June 2016 to the Princess Alexandra Hospital Head and Neck Multidisciplinary Meeting with UKP HNSCC from either presumed mucosal or cutaneous sites treated with curative intent were eligible. Patients with presumed mucosal origin were treated with radiation therapy (RT) with or without chemotherapy, while patients with presumed cutaneous SCC were treated with surgery and post-operative RT with or without chemotherapy. RESULTS A total of 63 patients met the inclusion criteria. Median follow up duration was 3.9 years (IQR 2.07-5.14). There were no subsequent primary site failures. The rate of nodal failure among presumed mucosal patients was 11.5%, and 8.1% among presumed cutaneous patients. The rate of distant metastatic failure was 11.1% among all patients. The estimated 5 year overall survival was 71.2% (95% CI 59.2-85.7%). CONCLUSION Treatment according to our pre-defined institutional policy for UKP HNSCC in a region with a high prevalence of cutaneous SCC appears to be safe and effective with low rates of mucosal primary emergence and nodal failure.

Deep inspiration breath hold in breast cancer: Development and analysis of a patient experience questionnaire

Evidence that Deep Inspiration Breath Hold (DIBH) can reduce cardiac dose during left‐sided breast radiation therapy (RT) has led to widespread uptake of this technology. There is a paucity of published information documenting the impact of this technique on the patients treatment experience. The aim of this study was to develop a tool to assess the patients experience with the introduction of DIBH using the Elekta® Active Breathing Coordinator (ABC) in a single institution.

A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care

Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB‐4], or enhanced liver fibrosis [ELF] test) are recommended as first‐line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB‐4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB‐4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06‐1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01‐1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. (Hepatology Communications 2018; 00:000‐000)

Improving plan quality for prostate volumetric-modulated arc therapy

We critically evaluated the quality and consistency of volumetric-modulated arc therapy (VMAT) prostate planning at a single institution to quantify objective measures for plan quality and establish clear guidelines for plan evaluation and quality assurance. A retrospective analysis was conducted on 34 plans generated on the Pinnacle3 version 9.4 and 9.8 treatment planning system to deliver 78 Gy in 39 fractions to the prostate only using VMAT. Data were collected on contoured structure volumes, overlaps and expansions, planning target volume (PTV) and organs at risk volumes and relationship, dose volume histogram, plan conformity, plan homogeneity, low-dose wash, and beam parameters. Standard descriptive statistics were used to describe the data. Despite a standardized planning protocol, we found variability was present in all steps of the planning process. Deviations from protocol contours by radiation oncologists and radiation therapists occurred in 12% and 50% of cases, respectively, and the number of optimization parameters ranged from 12 to 27 (median 17). This contributed to conflicts within the optimization process reflected by the mean composite objective value of 0.07 (range 0.01 to 0.44). Methods used to control low-intermediate dose wash were inconsistent. At the PTV rectum interface, the dose-gradient distance from the 74.1 Gy to 40 Gy isodose ranged from 0.6 cm to 2.0 cm (median 1.0 cm). Increasing collimator angle was associated with a decrease in monitor units and a single full 6 MV arc was sufficient for the majority of plans. A significant relationship was found between clinical target volume-rectum distance and rectal tolerances achieved. A linear relationship was determined between the PTV volume and volume of 40 Gy isodose. Objective values and composite objective values were useful in determining plan quality. Anatomic geometry and overlap of structures has a measurable impact on the plan quality achieved for prostate patients being treated with VMAT. By evaluating multiple planning variables, we have been able to determine important factors influencing plan quality and develop predictive models for quality metrics that have been incorporated into our new protocol and will be tested and refined in future studies.

Reducing radiotherapy waiting times for palliative patients: The role of the Advanced Practice Radiation Therapist

Palliative radiotherapy is effective in reducing symptom burden and improving quality of life in patients with symptomatic metastatic cancer and should be delivered in a timely manner. The aim of this study was to determine whether referring patients directly to a Palliative Advanced Practice Radiation Therapist (APRT) improves access to palliative radiotherapy and reduces time from referral to treatment.