Adaptive radiotherapy for virally mediated head and neck cancer : predicting which patients may benefit most

Background: Recent clinical studies have demonstrated an emerging subgroup of head and neck cancers that are virally mediated. This disease appears to be a distinct clinical entity with patients presenting younger and with more advanced nodal disease, having lower tobacco and alcohol exposure and highly radiosensitive tumours. This means they are living longer, often with the debilitating functional side effects of treatment. The primary objective of this study was to determine how virally mediated nasopharyngeal and oropharyngeal cancers respond to radiation therapy treatment. The aim was to determine risk categories and corresponding adaptive treatment management strategies to proactively manage these patients. Method/Results: 121 patients with virally mediated, node positive nasopharyngeal or oropharyngeal cancer who received radiotherapy treatment with curative intent between 2005 and 2010 were studied. Relevant patient demographics including age, gender, diagnosis, TNM stage, pre-treatment nodal size and dose delivered was recorded. Each patient’s treatment plan was reviewed to determine if another computed tomography (re-CT) scan was performed and at what time point (dose/fraction) this occurred. The justification for this re-CT was determined using four categories: tumour and/or nodal regression, weight loss, both or other. Patients who underwent a re-CT were further investigated to determine whether a new plan was calculated. If a re-plan was performed, the dosimetric effect was quantified by comparing dose volume histograms of planning target volumes and critical structures from the actual treatment delivered and the original treatment plan. Preliminary results demonstrated that 25/121 (20.7%) patients required a re-CT and that these re-CTs were performed between fractions 20 to 25 of treatment. The justification for these re-CTs consisted of a combination of tumour and/or nodal regression and weight loss. 16/25 (13.2%) patients had a replan calculated. 9 (7.4%) of these replans were implemented clinically due to the resultant dosimetric effect calculated. The data collected from this assessment was statistically analysed to identify the major determining factors for patients to undergo a re-CT and/or replan. Specific factors identified included nodal size and timing of the required intervention (i.e. how when a plan is to be adapted). This data was used to generate specific risk profiles that will form the basis of a biologically guided adaptive treatment management strategy for virally mediated head and neck cancer. Conclusion: Preliminary data indicates that virally mediated head and neck cancers respond significantly during radiation treatment (tumour and/or nodal regression and weight loss). Implications of this response are the potential underdosing or overdosing of tumour and/or surrounding critical structures. This could lead to sub-optimal patient outcomes and compromised quality of life. Consequently, the development of adaptive treatment strategies that improve organ sparing for this patient group is important to ensure delivery of the prescribed dose to the tumour volume whilst minimizing the dose received to surrounding critical structures. This could reduce side effects and improve overall patient quality of life. The risk profiles and associated adaptive treatment approaches developed in this study will be tested prospectively in the clinical setting in Phase 2 of this investigation.

Assessment of fundamental movement skills in childhood cancer patients

Background The improved treatment protocols and subsequent improved survival rates amongst childhood cancer patients has shifted the focus towards the long-term consequences arising from cancer treatment. Children who have completed cancer treatment are at a greater risk of delayed development, diminished functioning, disability, compromised fundamental movement skill (FMS) attainment and long term chronic health conditions. The aim of the study was to compare FMS of childhood cancer patients with an aged matched healthy reference group. Methods Pediatric cancer patients aged 5-8 years of age (n=26; median age 6.91 years), who completed cancer treatment (<5 years) at the Sydney Children’s Hospital were assessed performing 7 key FMS; sprint, side-gallop, vertical-jump, catch, over-arm throw, kick and leap. Results were compared to the reference group (n=430; 6.56 years). Results Childhood cancer patients scored significantly lower on 3 out of 7 FMS tests when compared to the reference group. These results equated to a significantly lower overall score for FMS. Conclusion This study highlighted the significant deficits in FMS within pediatric patients having completed cancer treatment. In order to reduce the occurrence of significant FMS deficits in this population, FMS interventions maybe warranted to assist in recovery from childhood cancer, prevent late effects and improve the quality of life in survivors of childhood cancer.

Lower limb biomechanical characteristics of patients with neuropathic diabetic foot ulcers: The diabetes foot ulcer study protocol

Background Foot ulceration is the main precursor to lower limb amputation in patients with type 2 diabetes worldwide. Biomechanical factors have been implicated in the development of foot ulceration; however the association of these factors to ulcer healing remains less clear. It may be hypothesised that abnormalities in temporal spatial parameters (stride to stride measurements), kinematics (joint movements), kinetics (forces on the lower limb) and plantar pressures (pressure placed on the foot during walking) contribute to foot ulcer healing. The primary aim of this study is to establish the biomechanical characteristics (temporal spatial parameters, kinematics, kinetics and plantar pressures) of patients with plantar neuropathic foot ulcers compared to controls without a history of foot ulcers. The secondary aim is to assess the same biomechanical characteristics in patients with foot ulcers and controls over-time to assess whether these characteristics remain the same or change throughout ulcer healing. Methods/Design The design is a case–control study nested in a six-month longitudinal study. Cases will be participants with active plantar neuropathic foot ulcers (DFU group). Controls will consist of patients with type 2 diabetes (DMC group) and healthy participants (HC group) with no history of foot ulceration. Standardised gait and plantar pressure protocols will be used to collect biomechanical data at baseline, three and six months. Descriptive variables and primary and secondary outcome variables will be compared between the three groups at baseline and follow-up. Discussion It is anticipated that the findings from this longitudinal study will provide important information regarding the biomechanical characteristic of type 2 diabetes patients with neuropathic foot ulcers. We hypothesise that people with foot ulcers will demonstrate a significantly compromised gait pattern (reduced temporal spatial parameters, kinematics and kinetics) at base line and then throughout the follow-up period compared to controls. The study may provide evidence for the design of gait-retraining, neuro-muscular conditioning and other approaches to off-load the limbs of those with foot ulcers in order to reduce the mechanical loading on the foot during gait and promote ulcer healing.

The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and its Association with Quality of Life in Ambulatory Patients Receiving Radiotherapy

OBJECTIVE: To evaluate the scored Patient-generated Subjective Global Assessment (PG-SGA) tool as an outcome measure in clinical nutrition practice and determine its association with quality of life (QoL). DESIGN: A prospective 4 week study assessing the nutritional status and QoL of ambulatory patients receiving radiation therapy to the head, neck, rectal or abdominal area. SETTING: Australian radiation oncology facilities. SUBJECTS: Sixty cancer patients aged 24-85 y. INTERVENTION: Scored PG-SGA questionnaire, subjective global assessment (SGA), QoL (EORTC QLQ-C30 version 3). RESULTS: According to SGA, 65.0% (39) of subjects were well-nourished, 28.3% (17) moderately or suspected of being malnourished and 6.7% (4) severely malnourished. PG-SGA score and global QoL were correlated (r=-0.66, P<0.001) at baseline. There was a decrease in nutritional status according to PG-SGA score (P<0.001) and SGA (P<0.001); and a decrease in global QoL (P<0.001) after 4 weeks of radiotherapy. There was a linear trend for change in PG-SGA score (P<0.001) and change in global QoL (P=0.003) between those patients who improved (5%) maintained (56.7%) or deteriorated (33.3%) in nutritional status according to SGA. There was a correlation between change in PG-SGA score and change in QoL after 4 weeks of radiotherapy (r=-0.55, P<0.001). Regression analysis determined that 26% of the variation of change in QoL was explained by change in PG-SGA (P=0.001). CONCLUSION: The scored PG-SGA is a nutrition assessment tool that identifies malnutrition in ambulatory oncology patients receiving radiotherapy and can be used to predict the magnitude of change in QoL.

Clinical Accuracy of the MedGem Indirect Calorimeter for Measuring Resting Energy Expenditure in Cancer Patients

OBJECTIVE: To compare, in patients with cancer and in healthy subjects, measured resting energy expenditure (REE) from traditional indirect calorimetry to a new portable device (MedGem) and predicted REE. DESIGN: Cross-sectional clinical validation study. SETTING: Private radiation oncology centre, Brisbane, Australia. SUBJECTS: Cancer patients (n = 18) and healthy subjects (n = 17) aged 37-86 y, with body mass indices ranging from 18 to 42 kg/m(2). INTERVENTIONS: Oxygen consumption (VO(2)) and REE were measured by VMax229 (VM) and MedGem (MG) indirect calorimeters in random order after a 12-h fast and 30-min rest. REE was also calculated from the MG without adjustment for nitrogen excretion (MGN) and estimated from Harris-Benedict prediction equations. Data were analysed using the Bland and Altman approach, based on a clinically acceptable difference between methods of 5%. RESULTS: The mean bias (MGN-VM) was 10% and limits of agreement were -42 to 21% for cancer patients; mean bias -5% with limits of -45 to 35% for healthy subjects. Less than half of the cancer patients (n = 7, 46.7%) and only a third (n = 5, 33.3%) of healthy subjects had measured REE by MGN within clinically acceptable limits of VM. Predicted REE showed a mean bias (HB-VM) of -5% for cancer patients and 4% for healthy subjects, with limits of agreement of -30 to 20% and -27 to 34%, respectively. CONCLUSIONS: Limits of agreement for the MG and Harris Benedict equations compared to traditional indirect calorimetry were similar but wide, indicating poor clinical accuracy for determining the REE of individual cancer patients and healthy subjects.

Correcting for bias when estimating the cost of hospital-acquired infection : an analysis of lower respiratory tract infections in non-surgical patients

Hospital acquired infections (HAI) are costly but many are avoidable. Evaluating prevention programmes requires data on their costs and benefits. Estimating the actual costs of HAI (a measure of the cost savings due to prevention) is difficult as HAI changes cost by extending patient length of stay, yet, length of stay is a major risk factor for HAI. This endogeneity bias can confound attempts to measure accurately the cost of HAI. We propose a two-stage instrumental variables estimation strategy that explicitly controls for the endogeneity between risk of HAI and length of stay. We find that a 10% reduction in ex ante risk of HAI results in an expected savings of £693 ($US 984).