Dion Forstner

Impact of a real-time peer review audit on patient management in a radiation oncology department.

In September 2006, the Royal Australian and New Zealand College of Radiologists (RANZCR) endorsed the modified Peer Review Audit Tool (PRAT). We aimed to assess the feasibility of using this tool in a busy radiation oncology department using an electronic medical record (EMR) system, identify areas of compliance and assess the impact of the audit process on patient management. Fortnightly random clinical audit was undertaken by using the revised RANZCR PRAT in the departments of radiation oncology at Liverpool and Macarthur Cancer Therapy Centres (LCTC and MCTC). Following audit of the EMR, treatment plans were audited by peer review. Data were collected prospectively from June 2007 to June 2008. Audits were carried out on 208 patients. Behaviour criteria were well documented in the EMR, but scanning of histology and medical imaging reports did not occur in up to a third of cases. With electronic prescriptions, treatment prescription errors were rare. In total, 8 (3.8%) out of 208 patients had a change to management recommended. Variability in interpretation of PRAT ‘protocol/study’ criteria was identified. We found that real‐time audit is feasible and effective in detecting both issues with documentation in the EMR, and a small number of patients in whom a change to management is recommended. Recommendations have been made in order to continue to improve the audit process including documentation of any changes recommended and whether the recommended change occurred.

Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer

There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow‐up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6‐targeted multiplex real‐time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow‐up. The HPV‐positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV‐positive group, after adjusting for clinicopathological factors, patients with cyclin D1‐positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1‐negative tumors. However, within the HPV‐negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes.

Effect of Intravenous Contrast on Treatment Planning System Dose Calculations in the Lung

Intravenous contrast-enhanced computed tomography is utilised in radiotherapy lung treatment planning to improve the delineation of the tumour volume and nodal areas. In the resultant CT images, the electron density is increased within the vascular structures of the lung and the overall density in the lung volume may also be increased. As yet, it is unclear whether the change in density affects the accuracy of dose calculations based on this CT data. Two investigations were undertaken. Firstly, contrast-enhancement was simulated using an anthropomorphic phantom. In the second investigation, bulk density corrections were performed in an existing patient dataset. In both investigations, treatment plans were generated using both pre- and post-contrast datasets. The numbers of monitor units calculated in each of the plans were compared, as were the resulting isodose curves, dose volume histograms and physical mean lung doses. The numbers of monitor units calculated from the contrast- and non contrast-enhanced datasets agreed within 2%. The isodose curves and dose volume histograms showed very minor differences in size and shape. With the introduction of contrast agent, the physical mean lung doses calculated remained below the limit recommended for an acceptable plan. These results indicate that the introduction of contrast agent has a minimal dosimetric impact upon lung cancer treatment plans.

How important is dosimetrist experience for intensity modulated radiation therapy? A comparative analysis of a head and neck case

PURPOSE Treatment planning for IMRT is a complex process that requires additional training and expertise. The aim of this study was to compare and analyze IMRT plans generated by dosimetrists with varying levels of IMRT planning experience. METHODS AND MATERIALS The computed tomography (CT) data of a patient previously treated with IMRT for left tonsillar carcinoma were used. The patients preexisting planning target volumes (PTVs) and all organs at risk were provided with the CT data set. Six dosimetrists with variable IMRT planning experience generated IMRT plans according to the departments protocol. Plan analysis included visual inspection and comparison of dose-volume histogram, conformity indices, treatment delivery efficiency, and dose delivery accuracy. RESULTS Visual review of the dose distribution showed that the 6 plans were comparable. However, only the 2 most experienced dosimetrists were able to meet the strict PTV aims and critical structure constraints. The least experienced dosimetrist had the worst planning outcome. Comparison of delivery efficiency showed that the number of segments, total monitor units, and treatment time increased as the IMRT planning experience decreased. CONCLUSIONS Dosimetrists with higher levels of IMRT planning experience produced a better quality head and neck IMRT plan. Different planning experience may need to be considered when organizing appropriate departmental resources.

Assessment of serial multi-parametric functional MRI (diffusion-weighted imaging and R2∗) with (18)F-FDG-PET in patients with head and neck cancer treated with radiation therapy

OBJECTIVE To evaluate the serial changes and correlations between readout-segmented technique with navigated phase correction diffusion-weighted MRI (DWI), R2*-MRI and (18)F-FDG positron emission tomography (PET) CT performed before and during radiation therapy (RT) in patients with mucosal primary head and neck cancer. METHODS The mean apparent diffusion coefficient (ADCmean) from DWI (at b = 50 and 800 s mm(-2)), the mean R2* values derived from T2(*)-MRI, and PET metabolic parameters, including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) were measured for the primary tumour. Spearman correlation coefficients were calculated to evaluate correlations between ADCmean, R2*, SUVmax, MTV and TLG. A paired t-test was performed to assess the MRI changes and the slope of serial MRI changes during RT. RESULTS Pre-treatment scans were performed in 28 patients and mid-treatment scans in 20 patients. No significant correlation was found between ADCmean and either R2* values or PET parameters. There were significant negative correlations of R2* values with pre-treatment PET parameters but not with mid-RT PET parameters: pre-SUVmax (p = 0.008), pre-MTV (p = 0.006) and pre-TLG (p = 0.008). A significant rise in ADCmean was found during the first half (p < 0.001) of RT but not in the second half (p = 0.215) of the treatment. There was an increase of the ADCmean values of 279.4 [95% confidence interval (95% CI): 210-348] in the first half of the treatment (Weeks 0-3). However, during the second-half period of treatment, the mean ADC value (Weeks 3-6) was 24.0 and the 95% CI (-40 to 88) included zero. This suggests that there was no significant change in ADC values during the second half of the treatment. CONCLUSION A significant negative correlation was found between pre-treatment R2*-MRI and PET parameters. DWI appeared to demonstrate potentially predictable changes during RT. ADVANCES IN KNOWLEDGE Understanding the correlation and changes that occur with time between potential imaging biomarkers may help us establish the most appropriate biomarkers to consider in future research.

Prognostic utility of 18F-FDG PET-CT performed prior to and during primary radiotherapy for nasopharyngeal carcinoma: Index node is a useful prognostic imaging biomarker site

PURPOSE To evaluate the prognostic value of (18)F-FDG-PET-CT performed prior to (prePET) and during the third week (iPET) of radiation therapy (RT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS Thirty-patients with newly diagnosed loco-regionally advanced NPC treated with radical RT underwent prePET and iPET. The median follow-up was 26months (8-66.9). The maximum-standardised-uptake-value (SUVmax), metabolic-tumour-volume (MTV) and total-lesional-glycolysis (TLG) of the primary tumour (PT), index-node (IN) (lymph node with highest TLG), total-lymph-nodes (TN) and combined primary-tumour and nodal (PTN), and their % reductions in iPET were analysed, and results were correlated with 2-year Kaplan-Meier loco-recurrence-free-survival (LRFS), regional-failure-free-survival (RFFS), distant-metastatic-failure-free-survival (DMFFS), disease-free-survival (DFS), and overall-survival (OS). Optimal-cutoffs (OC) were derived from Receiver-Operating-Characteristic curves. RESULTS For LRFS, the only predictor was reduction in PT MTV by >50%: 95.2% vs. 75.0%, p=0.024. For other treatment outcomes, only nodal or PTN predicted outcomes. The IN SUVmax (pre-PET-OC=10.45g/mL and iPET-OC=8.15) and TLG (prePET-OC=90g and iPET-OC=33.4) were the best predictors of outcome: RFFS (iPET SUVmax/TLG): 100% vs. 50%, p<0.001 and 100% vs. 44%, p=0.032; DMFFS (prePET SUVmax/TLG); 100% vs. 51.9%, p=0.004 and 100% vs. 47.6%, p=0.002; DFS (prePET TLG and iPET SUVmax): 87.5% vs. 33%, p=0.045 and 78.7% vs. 20%, p=0.01; and OS (prePET TLG): 100% vs 66.3%, p=0.036. CONCLUSIONS We have demonstrated IN of prePET and iPET to be a feasible and potentially useful novel imaging biomarker to predict for patients with NPC who have a high risk of regional or distant metastatic failure. Future work is required to validate our findings in a well-powered, prospective study with a standardised treatment protocol, and their potential use to guide individualised therapy for NPC.

A review of the predictive role of functional imaging in patients with mucosal primary head and neck cancer treated with radiation therapy

Advanced radiotherapy techniques, such as intensity‐modulated radiotherapy, have been reported to reduce toxicities by improving the dose conformity in mucosal primary head and neck cancer (MPHNC). However, to further optimize the therapeutic ratio, details on individual patient and disease characteristics may be necessary to tailor treatments. This is likely to include identifying poor responders for treatment intensification and good responders for de‐escalation strategies. Non‐invasive, repeatable imaging biomarkers are attractive modalities in both pre‐treatment and intra‐treatment response prediction with a view to individualized treatment options. This review has assessed the current literature on the prognostic/predictive role of widely available functional imaging (FI) studies such as fMRI(functional magnetic resonance imaging), functional computed tomography (fCT) and positron‐emission‐tomography(PET). A literature search was carried out using Medline, Embase and PubMed. Studies were included if imaging was undertaken pre and/or during radiotherapy (with or without the addition of chemotherapy and/or surgery). A total of 99 relevant studies were identified: 14 fMRI, 10 fCT, 59 FDG‐PET and 16 non‐FDG‐PET studies. These articles were reviewed to identify imaging parameters demonstrating a correlation with patient outcome or a factor considered to impact on patient outcome and thus likely to be of potential predictive value in MPHNC and associated future radiotherapy treatment directions. Several studies have demonstrated that both pre‐treatment and mid‐treatment FDG‐PET is predictive of outcomes. However, further studies are required to confirm the role of other imaging studies including fMRI and PET using other tracers. There is large heterogeneity within and between published studies, including tumour sites, treatment options, outcome endpoints and parameters assessed. We propose a minimum set of factors that should be reported and make recommendations for studies evaluating the predictive utility in MPHNC.

18F-FDG PET–CT performed before and during radiation therapy of head and neck squamous cell carcinoma : are they independent or complementary to each other?

The aims of this study are to evaluate the prognostic value of metabolic parameters derived from 18F‐FDG PET‐CT performed before definitive radiation therapy (RT) (prePET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to assess the additive prognostic values of FDG PET‐CT performed during RT (iPET).

The information needs of patients with head and neck cancer and their caregivers: a short report of instrument development and testing.

PURPOSE The study aimed to assess the reliability and scaling assumptions of an information needs questionnaire for patients with head and neck cancer (HNC) and their caregivers. BACKGROUND Patients with HNC have specific information needs but no tools exist that can simultaneously assess the needs among these patients and their caregivers. METHODS The Head and Neck Information Needs Questionnaire (HaNiQ) was adapted from a validated information needs questionnaire for breast cancer patients. Participants were recruited from two regionally-defined cancer services in NSW, Australia. Internal consistency reliability was assessed using Cronbachs alpha. Scaling assumptions, specifically item convergent and discriminant validity, were assessed using multi-trait scaling analysis. RESULTS The HaNiQ showed good internal consistency reliability for both patients and caregivers (Cronbachs alpha=0.94 for both) and scaling assumptions were met, with acceptable item convergent and discriminant validity. CONCLUSIONS The HaNiQ appears reliable, and would benefit from further testing.

Does Resilience Mediate Carer Distress After Head and Neck Cancer

Background: Caring for patients with head and neck cancer (HNC) can have significant negative psychological and practical impact; however, some carers seem able to cope effectively. Little research has investigated this resilience among carers. Objective: The objective of this study was to investigate the resilience levels among carers of patients with HNC. Methods: Carers (n = 51) from 2 cancer services in New South Wales completed the Resilience Scale (RS), the Head and Neck Information Needs Questionnaire, and the Hospital Anxiety and Depression Scale. Hospital Anxiety and Depression Scale cutoff scores (>8) were used to classify carers with clinically significant levels of anxiety or depression. Results: The majority of carers (67% [34/51]) reported moderately high to high resilience. Rates of anxiety and depression among carers were 27.4% and 9.8%, respectively. Higher resilience scores were significantly correlated with lower anxiety and depression scores, as well as increasing age. Resilience Scale scores were independent of the severity of the HNC. There were no significant correlations between RS scores and Head and Neck Information Needs Questionnaire scores. Finally, increasing RS scores were associated with a decreasing probability of possible anxiety or depression. Conclusions: These results indicate that higher resilience in carers of HNC patients was associated with lower levels of psychological distress. Further investigation into the relationship between resilience and carer psychological wellbeing is warranted. Implications for Practice: If further evidence supports the findings of this study, then investigating ways to build resilience will be an important clinical option for reducing carer morbidity associated with anxiety and depression. The RS could be used to assess resilience levels among carers of HNC patients.