Publications by authors named "Myo Min"

36 Publications

Prostate cancer GTV delineation with biparametric MRI and Ga-PSMA-PET: comparison of expert contours and semi-automated methods.

Br J Radiol 2021 Mar 28;94(1119):20201174. Epub 2021 Jan 28.

Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Australia.

Objective: The optimal method for delineation of dominant intraprostatic lesions (DIL) for targeted radiotherapy dose escalation is unclear. This study evaluated interobserver and intermodality variability of delineations on biparametric MRI (bpMRI), consisting of weighted (W) and diffusion-weighted (DWI) sequences, and Ga-PSMA-PET/CT; and compared manually delineated GTV contours with semi-automated segmentations based on quantitative thresholding of intraprostatic apparent diffusion coefficient (ADC) and standardised uptake values (SUV).

Methods: 16 patients who had bpMRI and PSMA-PET scanning performed prior to any treatment were eligible for inclusion. Four observers (two radiation oncologists, two radiologists) manually delineated the DIL on: (1) bpMRI (GTV), (2) PSMA-PET (GTV) and (3) co-registered bpMRI/PSMA-PET (GTV) in separate sittings. Interobserver, intermodality and semi-automated comparisons were evaluated against consensus Simultaneous Truth and Performance Level Estimation (STAPLE) volumes, created from the relevant manual delineations of all observers with equal weighting. Comparisons included the Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics.

Results: Interobserver agreement was significantly higher ( < 0.05) for GTV (DSC: 0.822, MDA: 1.12 mm) and GTV (DSC: 0.787, MDA: 1.34 mm) than for GTV (DSC: 0.705, MDA 2.44 mm). Intermodality agreement between GTV and GTV was low (DSC: 0.440, MDA: 4.64 mm). Agreement between semi-automated volumes and consensus GTV was low for MRI (DSC: 0.370, MDA: 8.16 mm) and significantly higher for PSMA-PET (0.571, MDA: 4.45 mm, < 0.05).

Conclusion: Ga-PSMA-PET appears to improve interobserver consistency of DIL localisation bpMRI and may be more viable for simple quantitative delineation approaches; however, more sophisticated approaches to semi-automatic delineation factoring for patient- and disease-related heterogeneity are likely required.

Advances In Knowledge: This is the first study to evaluate the interobserver variability of prostate GTV delineations with co-registered bpMRI and Ga-PSMA-PET.
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http://dx.doi.org/10.1259/bjr.20201174DOI Listing
March 2021

Capacity of National Malaria Control Programmes to implement vector surveillance: a global analysis.

Malar J 2020 Nov 23;19(1):422. Epub 2020 Nov 23.

Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.

Background: Solving the problem of malaria requires a highly skilled workforce with robust infrastructure, financial backing and sound programme management coordinated by a strategic plan. Here, the capacity of National Malaria Control Programmes (NMCPs) was analysed to identify the strengths and weaknesses underpinning the implementation of vector surveillance and control activities by the core elements of programme capacity, being strategic frameworks, financing, human resources, logistics and infrastructure, and information systems.

Results: Across nearly every country surveyed, the vector surveillance programmes were hampered by a lack of capacity and capability. Only 8% of NMCPs reported having sufficient capacity to implement vector surveillance. In contrast, 57%, 56% and 28% of NMCPs had the capacity to implement long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS) and larval source management (LSM) activities, respectively. Largely underlying this was a lack of up-to-date strategic plans that prioritize vector surveillance and include frameworks for decision-making and action.

Conclusions: Strategic planning and a lack of well-trained entomologists heavily hamper vector surveillance. Countries on the path to elimination generally had more operational/field staff compared to countries at the stage of control, and also were more likely to have an established system for staff training and capacity building. It is unlikely that controlling countries will make significant progress unless huge investments also go towards increasing the number and capacity of programmatic staff.
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http://dx.doi.org/10.1186/s12936-020-03493-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682121PMC
November 2020

Manual and semi-automated delineation of locally advanced rectal cancer subvolumes with diffusion-weighted MRI.

Br J Radiol 2020 Oct 2;93(1114):20200543. Epub 2020 Sep 2.

Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, QLD, Australia.

Objectives: To evaluate interobserver agreement for weighted (W) and diffusion-weighted MRI (DW-MRI) contours of locally advanced rectal cancer (LARC); and to evaluate manual and semi-automated delineations of restricted diffusion tumour subvolumes.

Methods: 20 cases of LARC were reviewed by 2 radiation oncologists and 2 radiologists. Contours of gross tumour volume (GTV) on W, DW-MRI and co-registered W/DW-MRI were independently delineated and compared using Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics of interobserver agreement. Restricted diffusion subvolumes within GTVs were manually delineated and compared to semi-automatically generated contours corresponding to intratumoral apparent diffusion coefficient (ADC) centile values.

Results: Observers were able to delineate subvolumes of restricted diffusion with moderate agreement (DSC 0.666, MDA 1.92 mm). Semi-automated segmentation based on the 40th centile intratumoral ADC value demonstrated moderate average agreement with consensus delineations (DSC 0.581, MDA 2.44 mm), with errors noted in image registration and luminal variation between acquisitions. A small validation set of four cases with optimised planning MRI demonstrated improvement (DSC 0.669, MDA 1.91 mm).

Conclusion: Contours based on co-registered W and DW-MRI could be used for delineation of biologically relevant tumour subvolumes. Semi-automated delineation based on patient-specific intratumoral ADC thresholds may standardise subvolume delineation if registration between acquisitions is sufficiently accurate.

Advances In Knowledge: This is the first study to evaluate the feasibility of semi-automated diffusion-based subvolume delineation in LARC. This approach could be applied to dose escalation or 'dose painting' protocols to improve delineation reproducibility.
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http://dx.doi.org/10.1259/bjr.20200543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548370PMC
October 2020

Cooking fuels use and carotid intima-media thickness during early pregnancy of women in Myanmar.

PLoS One 2020 29;15(7):e0236151. Epub 2020 Jul 29.

College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand.

Background: Fuels burned in households for cooking cause indoor air pollution, exposing those who are cooking. Despite the mounting evidence of the effects of fuels use on health, few studies focus on the effect of cooking fuels have on carotid intima-media thickness (CIMT), a surrogate atherosclerosis biomarker in the early stages of pregnancy. This study aimed to examine the association between the use of cooking fuels and CIMT during early trimester of pregnancy among cooking women in Myanmar.

Methodology: In this cross-sectional study, a part of an ongoing birth cohort analysis, a total of 192 cooking pregnant women over 18 years with gestational weeks less than 18 were recruited from 15 rural health centers in Nay Pyi Taw from September to November 2019. Sociodemographic data, residential data, and fuels use data were collected with semi-structured questionnaires in face-to-face interviews. Anthropometric, hemodynamic, blood lipids, and ultrasound CIMT measurements were performed under standard protocols. Multiple linear regression was modeled to explore associations.

Results: The study included 70 firewood fuel users, 26 charcoal fuel users, and 96 electricity fuel users. Following adjustments for potential confounding factors, firewood use was significantly associated with the increase of all CIMT analyzed. Importantly, a greater increase of mean CIMT of the right common carotid artery (RCCA; β = 0.033 mm; 95%CI: 0.006, 0.058; P<0.05) had significant association with charcoal use compared to firewood use (β = 0.029 mm; 95%CI: 0.010, 0.049; P<0.05).

Conclusions: Our findings demonstrate that the indoor use of cooking fuels that cause indoor air pollution, such as firewood and charcoal, is a considerable risk factor for human health and is associated with increased CIMT, wherein charcoal use contributes to more increase of mean CIMT of the RCCA. Measures to prevent health risks related to the use of such fuels should be instituted early on during pregnancy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236151PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390349PMC
September 2020

A global analysis of National Malaria Control Programme vector surveillance by elimination and control status in 2018.

Malar J 2019 Dec 4;18(1):399. Epub 2019 Dec 4.

Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.

Background: Maintaining the effectiveness of the currently recommended malaria vector control interventions while integrating new interventions will require monitoring key recommended indicators to identify threats to effectiveness including physiological and behavioural resistance to insecticides.

Methods: Country metadata on vector surveillance and control activities was collected using an online survey by National Malaria Control Programmes or partner organization officials. Country and regional surveillance activities were analysed for alignment with indicators for priority vector surveillance objectives recommended by the World Health Organization. Surveillance activities were also compared for countries in the E2020 (eliminating countries) and countries with more intense transmission.

Results: Significant differences in monitoring priority vector indicators between Africa and Asia-Pacific country programmes were found as well as differences between countries approaching elimination and those controlling malaria. Gaps were found between vector data collected and country management strategies (i.e., for insecticide resistance management and integrated vector control strategies) and for making programmatic decisions on surveillance and control using vector surveillance data.

Conclusions: Significant opportunities exist for increasing vector data collection on priority indicators and using these data for national programmatic decisions for both proactive insecticide resistance management and enhancing vector control.
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http://dx.doi.org/10.1186/s12936-019-3041-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894334PMC
December 2019

Radiation Oncology Quality Assessment Tool: A proposal for a new audit tool in modern radiation oncology.

J Med Imaging Radiat Oncol 2019 Oct 2;63(5):691-697. Epub 2019 Aug 2.

Department of Radiation Oncology, Sunshine Coast University Hospital, Sunshine Coast, Queensland, Australia.

Introduction: As a consequence of the development of improved treatment techniques and utilisation of digital records in radiation oncology, the RANZCR Peer Review Audit Tool has become outdated. The aim of this internal audit was to objectively evaluate the practice of our radiation oncology department to ensure that patients are being treated according to evidence-based national guidelines through the use of a new self-audit algorithm, the Radiation Oncology Quality Assessment Tool (ROQAT).

Methods: Using ROQAT, a retrospective audit was conducted of patients who received definitive treatment within the first six months (June 2017-November 2017) of opening a new radiation oncology department at the Sunshine Coast University Hospital. Data were collected from MOSAIQ and electronic medical records.

Results: Two hundred and six patients were included. The median age was 65 years. Most commonly treated tumour streams included: breast (n = 62), skin (n = 31), colorectal (n = 25), genitourinary (n = 21) and head and neck (n = 21). Documentation was complete for all patients. Seventy-four per cent of patients were discussed in a multidisciplinary team meeting. Fifty-five per cent of patients were treated with inverse planning techniques. Treatment with radiation therapy was indicated in 97% of patients. Dose and fractionation were concordant with protocols in 83% of cases. Thirty-nine per cent received concurrent chemotherapy, and of these, 93% were in accordance with protocols. More than 50% were treated according to published delineation protocols.

Conclusion: The ROQAT is a proposal for a new audit tool that reflects modern radiation therapy practice, with emphasis on compliance with evidence-based guidelines.
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http://dx.doi.org/10.1111/1754-9485.12928DOI Listing
October 2019

Evaluating diffusion-weighted magnetic resonance imaging for target volume delineation in head and neck radiotherapy.

J Med Imaging Radiat Oncol 2019 Jun 28;63(3):399-407. Epub 2019 Feb 28.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.

Introduction: Inter-observer variability (IOV) in target volume delineation is a source of error in head and neck radiotherapy. Diffusion-weighted imaging (DWI) has been shown to be useful in detecting recurrent head and neck cancer. This study aims to determine whether DWI improves target volume delineation and IOV.

Methods: Four radiation oncologists delineated the gross tumour volume (GTV) for ten head and neck cancer patients. Delineation was performed on CT alone as well as fused image sets which incorporated fluorodeoxyglucose (FDG)-positron emission tomography (PET) and magnetic resonance imaging (MRI) in the form of CT/PET, CT/PET/T2W and CT/PET/T2W/DWI image sets. Analysis of the variability of contour volumes was completed by comparison to the simultaneous truth and performance level estimation (STAPLE) volumes. The DICE Similarity Coefficient (DSC) and other IOV metrics for each observer's contour were compared to the STAPLE for each patient and image dataset. A DWI usability scoresheet for delineation was completed.

Results: The CT/PET/T2W/DWI mean GTV volume of 13.37 (10.35-16.39)cm was shown to be different to the mean GTV of 10.92 (8.32-13.51)cm when using CT alone (P < 0.001). The GTV DSC amongst observers for CT alone was 0.72 (0.65-0.79), CT/PET was 0.73 (0.67-0.80), CT/PET/T2W was 0.71 (0.64-0.77) and CT/PET/T2W/DWI was 0.69 (0.61-0.75).

Conclusion: Mean GTVs with the addition of DWI had slightly larger volumes compared to standard CT and CT/PET volumes. DWI may add supplemental visual information for GTV delineation while having a small impact on IOV, therefore potentially improving target volume delineation.
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http://dx.doi.org/10.1111/1754-9485.12866DOI Listing
June 2019

Referral rates to multidisciplinary team meetings: Is there disparity between tumour streams?

J Med Imaging Radiat Oncol 2019 Jun 8;63(3):378-382. Epub 2019 Jan 8.

Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia.

Introduction: The multidisciplinary team meeting (MDTM) approach is accepted as standard of care to optimise treatment for patients diagnosed with cancer. This retrospective audit reviews the proportion of patients whose care is being discussed at cancer MDTMs within the Sunshine Coast Hospital and Health Service (SCHHS).

Methods: Patients included were those diagnosed with cancer within the SCHHS between 2010 and 2015, and subsequently referred to a public MDTM for discussion. Data were extracted from the Queensland Cancer Control Analysis Team (QCCAT) database regarding the incidence of breast, lung, upper gastrointestinal (GI), colorectal, genitourinary and malignant haematological cancers and the number of patients referred to the corresponding MDTM.

Results: Data from 2015 show referral rates to MDTMs as follows: lung 100%, upper gastrointestinal 100%, colorectal 64%, breast 60%, malignant haematology 40% and genitourinary 28%. Of the genitourinary presentations, 70% were prostate cases and 14% bladder cases. Review of genitourinary MDTM outcomes found that, of the patients with prostate cancer discussed, 30% were metastatic, 19% were poor surgical candidates and 15% had biochemical recurrence.

Conclusion: This audit demonstrates variable utilisation of MDTMs between tumour streams. Our study shows a high and increasing referral rate to all tumour stream MDTMs except for genitourinary. This suggests a possible underutilisation of genitourinary MDTMs to discuss treatment options for patients with genitourinary cancer. Collaborative research is warranted to further investigate whether this is a local or widespread issue.
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http://dx.doi.org/10.1111/1754-9485.12851DOI Listing
June 2019

Perceived role and its enhancing factors among the village health volunteers regarding malaria control in rural myanmar.

Indian J Public Health 2018 Jan-Mar;62(1):10-14

Dr and Programme Manager, Asia Pacific Malaria Elimination Network, Singapore.

Background: Village health volunteers (VHVs) are key agents for malaria control in community. The Myanmar Medical Association-Malaria (MMA-Malaria) Project has promoted effective malaria control in endemic and high-risk townships by supporting roles of VHVs.

Objectives: To assess the roles of VHVs on malaria control and factors enhancing their roles in rural Myanmar.

Methods: : A cross-sectional study was conducted in five townships where the MMA-Malaria Project has been implemented. One hundred and fifty VHVs were sampled from five townships by simple random sampling. Data were collected by trained interviewers using structured questionnaires, which covered sociodemographic, supportive, motivational factors, and roles of malaria control. Studied variables were described by proportions, means, and standard deviations and were analyzed for their association by odds ratio with 95% confidence interval and Chi-square tests.

Results: Most of VHVs (96%) expected to demonstrate good roles on malaria control, but only 44.0% exhibited current roles at a good level. Factors enhancing their roles were female (P = 0.037), family income ≥50,001 kyat/month (P < 0.015), time serving as a volunteer 1-2 years (P = 0.006), good knowledge of malaria control (P < 0.001), good family support (P < 0.001), good community support (P < 0.001), and good motivational factors (P = 0.002).

Conclusion: VHVs are key agents for malaria control in community. Most of VHVs expected to demonstrate good roles on malaria control, but less than half of them exhibited current roles at a good level. The systems and program for improving VHVs' knowledge, encouraging family and community support, and promoting motivation are essential for their better roles.
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http://dx.doi.org/10.4103/ijph.IJPH_432_16DOI Listing
September 2019

Quality Testing of Artemisinin-Based Antimalarial Drugs in Myanmar.

Am J Trop Med Hyg 2017 Oct 18;97(4):1198-1203. Epub 2017 Aug 18.

Department of Entomology, Pennsylvania State University, University Park, Pennsylvania.

Artemisinin-based combination therapies are the frontline treatment of malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices. A subset of these samples was further tested by high-performance liquid chromatography (HPLC). This survey identified that > 35% of the collected drugs were oral artesunate and artemether monotherapies. When tested with the dipsticks, all but one sample passed the assays, indicating that the detected artemisinin derivative content corresponded approximately to the labeled contents. However, one artesunate injection sample was found to contain no active ingredient at all by the dipstick assay and subsequent HPLC analysis. The continued circulation of oral monotherapies and the description, for the first time, of falsified parenteral artesunate provides a worrisome picture of the antimalarial drug quality in Myanmar during the malaria elimination phase, a situation that deserves more oversight from regulatory authorities.
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http://dx.doi.org/10.4269/ajtmh.17-0305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637622PMC
October 2017

Multiparametric magnetic resonance imaging in mucosal primary head and neck cancer: a prospective imaging biomarker study.

BMC Cancer 2017 Jul 10;17(1):475. Epub 2017 Jul 10.

Department of Radiation Oncology, Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.

Background: Radical radiotherapy, with or without concomitant chemotherapy forms the mainstay of organ preservation approaches in mucosal primary head and neck cancer. Despite technical advances in cancer imaging and radiotherapy administration, a significant proportion of patients fail to achieve a complete response to treatment. For those patients who do achieve a complete response, acute and late toxicities remain a cause of morbidity. A critical need therefore exists for imaging biomarkers which are capable of informing patient selection for both treatment intensification and de-escalation strategies.

Methods/design: A prospective imaging study has been initiated, aiming to recruit patients undergoing radical radiotherapy (RT) or chemoradiotherapy (CRT) for mucosal primary head and neck cancer (MPHNC). Eligible patients are imaged using FDG-PET/CT before treatment, at the end of week 3 of treatment and 12 weeks after treatment completion according to local imaging policy. Functional MRI using diffusion weighted (DWI), blood oxygen level-dependent (BOLD) and dynamic contrast enhanced (DCE) sequences is carried out prior to, during and following treatment. Information regarding treatment outcomes will be collected, as well as physician-scored and patient-reported toxicity.

Discussion: The primary objective is to determine the correlation of functional MRI sequences with tumour response as determined by FDG-PET/CT and clinical findings at 12 weeks post-treatment and with local control at 12 months post-treatment. Secondary objectives include prospective correlation of functional MRI and PET imaging with disease-free survival and overall survival, defining the optimal time points for functional MRI assessment of treatment response, and determining the sensitivity and specificity of functional MRI sequences for assessment of potential residual disease following treatment. If the study is able to successfully characterise tumours based on their functional MRI scan characteristics, this would pave the way for further studies refining treatment approaches based on prognostic and predictive imaging data.

Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616000534482 (26 April 2016).
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http://dx.doi.org/10.1186/s12885-017-3448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502487PMC
July 2017

Local Sphingosine Kinase 1 Activity Improves Islet Transplantation.

Diabetes 2017 05 7;66(5):1301-1311. Epub 2017 Feb 7.

Discipline of Medicine, The University of Adelaide, Adelaide, Australia

Pancreatic islet transplantation is a promising clinical treatment for type 1 diabetes, but success is limited by extensive β-cell death in the immediate posttransplant period and impaired islet function in the longer term. Following transplantation, appropriate vascular remodeling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase (SK) pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown. We observed that donor islets from mice deficient in SK1 ( knockout) contain a reduced number of resident intraislet vascular endothelial cells. Furthermore, we demonstrate that the main product of SK1, sphingosine-1-phosphate, controls the migration of intraislet endothelial cells in vitro. We reveal in vivo that knockout islets have an impaired ability to cure diabetes compared with wild-type controls. Thus, SK1-deficient islets not only contain fewer resident vascular cells that participate in revascularization, but likely also a reduced ability to recruit new vessels into the transplanted islet. Together, our data suggest that SK1 is important for islet revascularization following transplantation and represents a novel clinical target for improving transplant outcomes.
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http://dx.doi.org/10.2337/db16-0837DOI Listing
May 2017

Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers.

Eur J Nucl Med Mol Imaging 2017 May 21;44(5):801-811. Epub 2016 Dec 21.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.

Purpose: To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC).

Methods: This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 - 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed.

Results: Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS p = 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS p = 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (p = 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (p = 0.026, 0.003 and 0.014, respectively). There were no significant correlations between oncological outcomes and prePET nodal parameters.

Conclusion: We demonstrated that the index node and total node SUVmean on iPET and a reduction of more than 50 % in MTV and TLG are useful imaging biomarkers, and can potentially identify those patients with MPHNSCC who have a high risk of locoregional metastatic failure and death.
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http://dx.doi.org/10.1007/s00259-016-3584-1DOI Listing
May 2017

Malaria incidence in Myanmar 2005-2014: steady but fragile progress towards elimination.

Malar J 2016 Oct 18;15(1):503. Epub 2016 Oct 18.

University of Medicine 2, Yangon, Myanmar.

Background: There has been an impressive recent reduction in the global incidence of malaria, but the development of artemisinin resistance in the Greater Mekong Region threatens this progress. Increasing artemisinin resistance is particularly important in Myanmar, as it is the country in the Greater Mekong Region with the greatest malaria burden. If malaria is to be eliminated in the region, it is essential to define the spatial and temporal epidemiology of the disease in Myanmar to inform control strategies optimally.

Results: Between the years 2005 and 2014 there was an 81.1 % decline in the reported annual incidence of malaria in Myanmar (1341.8 cases per 100,000 population to 253.3 cases per 100,000 population). In the same period, there was a 93.5 % decline in reported annual mortality from malaria (3.79 deaths per 100,000 population to 0.25 deaths per 100,000 population) and a 87.2 % decline in the proportion of hospitalizations due to malaria (7.8 to 1.0 %). Chin State had the highest reported malaria incidence and mortality at the end of the study period, although socio-economic and geographical factors appear a more likely explanation for this finding than artemisinin resistance. The reduced malaria burden coincided with significant upscaling of disease control measures by the national government with support from international partners. These programmes included the training and deployment of over 40,000 community health care workers, the coverage of over 60 % of the at-risk population with insecticide-treated bed nets and significant efforts to improve access to artemesinin-based combination treatment. Beyond these malaria-specific programmes, increased general investment in the health sector, changing population demographics and deforestation are also likely to have contributed to the decline in malaria incidence seen over this time.

Conclusions: There has been a dramatic fall in the burden of malaria in Myanmar since 2005. However, with the rise of artemisinin resistance, continued political, financial and scientific commitment is required if the ambitious goal of malaria elimination in the country is to be realized.
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http://dx.doi.org/10.1186/s12936-016-1567-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069869PMC
October 2016

Uncertainties in volume delineation in radiation oncology: A systematic review and recommendations for future studies.

Radiother Oncol 2016 11 8;121(2):169-179. Epub 2016 Oct 8.

Cancer Therapy Centre, Liverpool Hospital, Australia; South Western Sydney Clinical School, University of New South Wales, Australia; Ingham Institute of Applied Medical Research, Liverpool Hospital, Australia; Centre for Medical Radiation Physics, University of Wollongong, Australia.

Background And Purpose: Volume delineation is a well-recognised potential source of error in radiotherapy. Whilst it is important to quantify the degree of interobserver variability (IOV) in volume delineation, the resulting impact on dosimetry and clinical outcomes is a more relevant endpoint. We performed a literature review of studies evaluating IOV in target volume and organ-at-risk (OAR) delineation in order to analyse these with respect to the metrics used, reporting of dosimetric consequences, and use of statistical tests.

Methods And Materials: Medline and Pubmed databases were queried for relevant articles using keywords. We included studies published in English between 2000 and 2014 with more than two observers.

Results: 119 studies were identified covering all major tumour sites. CTV (n=47) and GTV (n=38) were most commonly contoured. Median number of participants and data sets were 7 (3-50) and 9 (1-132) respectively. There was considerable heterogeneity in the use of metrics and methods of analysis. Statistical analysis of results was reported in 68% (n=81) and dosimetric consequences in 21% (n=25) of studies.

Conclusion: There is a lack of consistency in conducting and reporting analyses from IOV studies. We suggest a framework to use for future studies evaluating IOV.
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http://dx.doi.org/10.1016/j.radonc.2016.09.009DOI Listing
November 2016

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

J Med Imaging Radiat Oncol 2017 Feb 28;61(1):99-123. Epub 2016 Jul 28.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.

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.
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http://dx.doi.org/10.1111/1754-9485.12496DOI Listing
February 2017

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

Radiother Oncol 2016 07 16;120(1):87-91. Epub 2016 Jun 16.

Cancer Therapy Centre, Liverpool Hospital, Australia.

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.
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http://dx.doi.org/10.1016/j.radonc.2016.05.021DOI Listing
July 2016

A review of interventions to reduce inter-observer variability in volume delineation in radiation oncology.

J Med Imaging Radiat Oncol 2016 Jun 11;60(3):393-406. Epub 2016 May 11.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.

Introduction: Inter-observer variability (IOV) in target volume and organ-at-risk (OAR) delineation is a source of potential error in radiation therapy treatment. The aims of this study were to identify interventions shown to reduce IOV in volume delineation.

Methods: Medline and Pubmed databases were queried for relevant articles using various keywords to identify articles which evaluated IOV in target or OAR delineation for multiple (>2) observers. The search was limited to English language articles and to those published from 1 January 2000 to 31 December 2014. Reference lists of identified articles were scrutinised to identify relevant studies. Studies were included if they reported IOV in contouring before and after an intervention including the use of additional or alternative imaging.

Results: Fifty-six studies were identified. These were grouped into evaluation of guidelines (n = 9), teaching (n = 9), provision of an autocontour (n = 7) and the impact of imaging (n = 31) on IOV. Guidelines significantly reduced IOV in 7/9 studies. Teaching interventions reduced IOV in 8/9 studies, statistically significant in 4. The provision of an autocontour improved consistency of contouring in 6/7 studies, statistically significant in 5. The effect of additional imaging on IOV was variable. Pre-operative CT was useful in reducing IOV in contouring breast and liver cancers, PET scans in lung cancer, rectal cancer and lymphoma and MRI scans in OARs in head and neck cancers.

Conclusion: Inter-observer variability in volume delineation can be reduced with the use of guidelines, provision of autocontours and teaching. The use of multimodality imaging is useful in certain tumour sites.
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http://dx.doi.org/10.1111/1754-9485.12462DOI Listing
June 2016

Assessment of MRI image quality for various setup positions used in breast radiotherapy planning.

Radiother Oncol 2016 04 9;119(1):57-60. Epub 2016 Mar 9.

Liverpool and Macarthur Cancer Therapy Centres, Australia; Ingham Institute of Applied Medical Research, Australia; South Western Clinical School, University of New South Wales, Australia; Centre for Medical Radiation Physics, University of Wollongong, Australia; Institute of Medical Physics, School of Physics, University of Sydney, Australia.

This study investigates breast magnetic resonance imaging (MRI) image quality for 3 different breast radiotherapy positions (prone, supine flat and supine inclined) and associated choice of breast coils. Supine breast MRI has comparable image quality to prone breast MRI for the purposes of radiotherapy delineation for T2-weighted sequences.
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http://dx.doi.org/10.1016/j.radonc.2016.02.024DOI Listing
April 2016

Positive deviance as a novel tool in malaria control and elimination: methodology, qualitative assessment and future potential.

Malar J 2016 Feb 16;15:91. Epub 2016 Feb 16.

Malaria Consortium Asia, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajavidhi Road, Bangkok, 10400, Thailand.

Background: Positive deviance (PD) is an asset-based, community-driven approach to behaviour change that has successfully been applied to address many health and social problems. It is yet to have been assessed for malaria control but may represent a promising tool for malaria elimination given its suitability in targeting small and remote population groups, apparent sustainability and ability to instil a high amount of community mobilisation. Here, the PD methodology as applied to malaria is explained, with focus upon and qualitative assessment of a proof of concept study in Cambodia.

Methods: Three villages in Battambang, northwestern Cambodia were selected for the intervention, with an estimated population of 5036 including both residents and migrant workers. In August 2010, field teams conducted a 1 week PD process to sensitise and mobilise the community, establish normative behaviours in relation to malaria control and prevention, identify positive deviant behaviours from within the community, and identify PD volunteers. Until March 2011, PD volunteers were supported by field teams via monthly meetings to conduct activities in their respective communities to increase practice of PD behaviours. In February 2012, 1 year following the end of external support, evaluative interviews were conducted with community members to qualitatively assess community acceptance and interpretation of the PD intervention, perceived behaviour changes, and perceived positive outcomes.

Results: Qualitative data from focus group discussions and in-depth interviews showed that the PD approach was well-accepted into the communities and created a strong sense of community empowerment. Positive behaviour change was linked to the PD intervention, including greater usage of nets by forest goers, and use of public health facilities for malaria diagnosis and treatment. One year following the end of external assistance, PD volunteers were still conducting activities in their respective communities.

Conclusions: PD offers a promising tool in malaria control and elimination settings. Work is ongoing to quantitatively measure impact of PD on behaviours and malaria transmission and once gathered, national malaria control programmes should be encouraged to look at including PD as part of their national strategies. Feasibility of scale-up, cost-effectiveness, and applicability to other settings and diseases is also currently being explored.
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http://dx.doi.org/10.1186/s12936-016-1129-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754848PMC
February 2016

Rapid evaluation of artesunate quality with a specific monoclonal antibody-based lateral flow dipstick.

Anal Bioanal Chem 2016 Sep 12;408(22):6003-8. Epub 2016 Feb 12.

Department of Entomology, Pennsylvania State University, University Park, PA, 16802, USA.

Artesunate is a frontline antimalarial drug for treating Plasmodium falciparum malaria. To produce specific antibodies to artesunate, the carboxyl group of artesunate was directly conjugated to carrier protein as the immunogen. A specific monoclonal antibody (mAb) 3D82G6 against artesunate was obtained by high-throughput screening of positive hybridoma clones. This monoclonal antibody had 4.0, 0.5, and 0.9 % cross reactivities with artemisinin, dihydroartemisinin, and artemether, respectively. A dipstick immunoassay was developed, and the indicator range for artesunate was 1000-2000 ng mL(-1). No interference was observed with artemisinin, dihydroartemisinin, artemether, and other commonly used antimalarial drugs for up to 20,000 ng mL(-1). The dipsticks were used for determination of artesunate contents in commercial drugs, and the results were agreeable with those determined by high-performance liquid chromatography. This dipstick, with its specificity and sensitivity for artesunate and simplicity to use, makes it a potential point-of-care device for rapid quality evaluation of artesunate-containing antimalarial drugs. Graphical Abstract Specific monoclonal antibody-based lateral flow dipstick for artesunate.
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http://dx.doi.org/10.1007/s00216-016-9363-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982846PMC
September 2016

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?

J Med Imaging Radiat Oncol 2016 Jun 12;60(3):433-40. Epub 2016 Feb 12.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.

Introduction: The aims of this study are to evaluate the prognostic value of metabolic parameters derived from (18) F-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).

Methods: One hundred patients with MPHNSCC treated with radical RT underwent staging prePET and iPET performed during the third week of treatment. The maximum standardized uptake value (SUVmax ), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary tumour were analysed for both prePET and iPET, and results were correlated with loco-regional recurrence-free survival (LRFS), disease-free survival (DFS), metastatic failure-free survival (MFFS) and overall survival (OS), using Kaplan-Meier analysis. Optimal cut-offs (OC) for prePET and iPET were derived from Receiver Operating Characteristic curves. Patients with metabolic parameters above/below the individual OC of prePET as well as iPET (i.e. combined prePET and iPET (comPET)) were evaluated against their outcomes.

Results: Median age was 61 years (range 39-81), median follow-up of 20 months (range 4-70, mean 27), and AJCC 7th Edition clinical stage II, III and IV were 8, 24 and 68 patients respectively. Metabolic values below individual OC in comPET were found to be associated with statistically significant improvements (P < 0.05) in DFS, LRFS and OS. In addition, patients with SUVmax above the OC in comPET were associated with worse MFFS (P = 0.011) and confirmed on both univariate (P = 0.019) and multivariate analyses (P = 0.04).

Conclusion: Addition of iPET significantly improves the prognostic values of all three metabolic parameters and can potentially be used in future adaptive local and systemic therapy trials.
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http://dx.doi.org/10.1111/1754-9485.12439DOI Listing
June 2016

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.

Br J Radiol 2016 9;89(1058):20150530. Epub 2015 Dec 9.

1 Department of Radiation Oncology, Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.

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.
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http://dx.doi.org/10.1259/bjr.20150530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985201PMC
May 2016

The Safety of a Conservative Fluid Replacement Strategy in Adults Hospitalised with Malaria.

PLoS One 2015 18;10(11):e0143062. Epub 2015 Nov 18.

Menzies School of Health Research, Charles Darwin University, Darwin, Australia.

Background: A conservative approach to fluid resuscitation improves survival in children with severe malaria; however, this strategy has not been formally evaluated in adults with the disease.

Methods: Adults hospitalised with malaria at two tertiary referral hospitals in Myanmar received intravenous fluid replacement with isotonic saline, administered at a maintenance rate using a simple weight-based algorithm. Clinical and biochemical indices were followed sequentially.

Results: Of 61 adults enrolled, 34 (56%) had Plasmodium falciparum mono-infection, 17 (28%) Plasmodium vivax mono-infection and 10 (16%) mixed infection; 27 (44%) patients were at high risk of death (P. falciparum infection and RCAM score ≥ 2). In the first six hours of hospitalisation patients received a mean 1.7 ml/kg/hour (range: 1.3-2.2) of intravenous fluid and were able to drink a mean of 0.8 ml/kg/hour (range: 0-3). Intravenous fluid administration and oral intake were similar for the remainder of the first 48 hours of hospitalisation. All 61 patients survived to discharge. No patient developed Adult Respiratory Distress Syndrome, a requirement for renal replacement therapy or hypotension (mean arterial pressure < 60 mmHg). Plasma lactate was elevated (> 2 mmol/L) on enrolment in 26 (43%) patients but had declined by 6 hours in 25 (96%) and was declining at 24 hours in the other patient. Plasma creatinine was elevated (> 120 μmol/L) on enrolment in 17 (28%) patients, but was normal or falling in 16 (94%) at 48 hours and declining in the other patient by 72 hours. There was no clinically meaningful increase in plasma lactate or creatinine in any patient with a normal value on enrolment. Patients receiving fluid replacement with the conservative fluid replacement algorithm were more likely to survive than historical controls in the same hospitals who had received fluid replacement guided by clinical judgement in the year prior to the study (p = 0.03), despite having more severe disease (p < 0.001).

Conclusions: A conservative fluid resuscitation strategy appears safe in adults hospitalised with malaria.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143062PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651424PMC
June 2016

Prognostic role of metabolic parameters of (18)F-FDG PET-CT scan performed during radiation therapy in locally advanced head and neck squamous cell carcinoma.

Eur J Nucl Med Mol Imaging 2015 Dec 17;42(13):1984-94. Epub 2015 Jun 17.

Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, 2170, Australia.

Purpose: To evaluate the prognostic value of (18)F-FDG PET-CT performed in the third week (iPET) of definitive radiation therapy (RT) in patients with newly diagnosed locally advanced mucosal primary head and neck squamous-cell-carcinoma (MPHNSCC).

Methodology: Seventy-two patients with MPHNSCC treated with radical RT underwent staging PET-CT and iPET. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary tumour (PT) and index node (IN) [defined as lymph node(s) with highest TLG] were analysed, and results were correlated with loco-regional recurrence-free survival (LRFS), disease-free survival (DFS), metastatic failure-free survival(MFFS) and overall survival (OS), using Kaplan-Meier analysis.

Results: Optimal cutoffs (OC) were derived from receiver operating characteristic curves: SUVmax-PT = 4.25 g/mL, MTVPT = 3.3 cm(3), TLGPT = 9.4 g, for PT, and SUVmax-IN = 4.05 g/mL, MTVIN = 1.85 cm(3) and TLGIN = 7.95 g for IN. Low metabolic values in iPET for PT below OC were associated with statistically significant better LRFS and DFS. TLG was the best predictor of outcome with 2-year LRFS of 92.7 % vs. 71.1% [p = 0.005, compared with SUVmax (p = 0.03) and MTV (p = 0.022)], DFS of 85.9% vs. 60.8% [p = 0.005, compared with SUVmax (p = 0.025) and MTV (p = 0.018)], MFFS of 85.9% vs. 83.7% [p = 0.488, compared with SUVmax (p = 0.52) and MTV (p = 0.436)], and OS of 81.1% vs. 75.0% [p = 0.279, compared with SUVmax (p = 0.345) and MTV (p = 0.512)]. There were no significant associations between the percentage reduction of primary tumour metabolic parameters and outcomes. In patients with nodal disease, metabolic parameters below OC (for both PT and IN) were significantly associated with all oncological outcomes, while TLG was again the best predictor: LRFS of 84.0% vs. 55.3% (p = 0.017), DFS of 79.4% vs. 38.6% (p = 0.001), MFFS 86.4% vs. 68.2% (p = 0.034) and OS 80.4% vs. 55.7% (p = 0.045).

Conclusion: The metabolic parameters of iPET can be useful predictors of patient outcome and potentially have a role in adaptive therapy for MPHNSCC. Among the three parameters, TLG was found to be the best prognostic indicator of oncological outcomes.
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http://dx.doi.org/10.1007/s00259-015-3104-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623084PMC
December 2015

The prognostic utility of bedside assessment of adults hospitalized with malaria in Myanmar: a retrospective analysis.

Malar J 2015 Feb 7;14:63. Epub 2015 Feb 7.

Menzies School of Health Research, Charles Darwin University, Darwin, Australia.

Background: Data collected in clinical trials have been used to develop scoring systems that identify adults with malaria at greatest risk of death. One of these, the RCAM score, can be simply determined by measuring a patient's Glasgow Coma Score and respiratory rate on admission to hospital. However the safety of using the RCAM score to define high-risk patients has not been assessed outside of the clinical trial setting.

Methods: A retrospective audit of medical records of all adults admitted with a diagnosis of malaria to two tertiary referral hospitals in Lower Myanmar in 2013 was undertaken. An RCAM score was calculated in all patients and related to their subsequent clinical course.

Results: The recent decline in malaria hospitalizations at both sites continued in 2013. During the year 90 adults were hospitalized with malaria; 62 (69%) had Plasmodium falciparum mono-infection, 11 (12%) had Plasmodium vivax mono-infection, 17 (19%) had mixed infection. All seven (7.7%) deaths occurred in patients infected with P. falciparum. An admission RCAM score <2 identified all the patients that would survive to discharge (positive predictive value (95% confidence interval (CI)) 100% (94.9-100%) and also predicted a requirement for less supportive care: 9/70 (13%) patients with an admission RCAM score <2 required supportive care (blood transfusion, vasopressor support or oxygen supplementation) during their hospitalization compared with 12/20 (60%) patients with an admission RCAM score ≥2 (p < 0.0001). No patient with P. vivax mono-infection required supportive care during their hospitalization. Patients with an oxygen saturation ≤95% on room air on admission were more likely to die before discharge (odds ratio 17.3 (95% CI: 2.9-101.2) than patients with a higher oxygen saturation (p = 0.002).

Conclusions: Even outside a clinical trial setting the RCAM score reliably identifies adults with malaria who are at greatest risk of death and can be safely used in the initial triage and management of these patients.
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http://dx.doi.org/10.1186/s12936-015-0549-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323221PMC
February 2015

Are staging investigations being overused in patients with low and intermediate risk prostate cancer?

J Med Imaging Radiat Oncol 2015 Feb 4;59(1):77-81. Epub 2014 Sep 4.

Department of Radiation Oncology, Royal Adelaide Hospital, South Australia, Australia.

Introduction: According to international best practice guidelines, staging abdominal and pelvic computed tomography (CTAP) and whole body bone scan (WBBS) are not recommended for asymptomatic low and intermediate-risk prostate cancer. Despite this, many patients undergo these investigations. Our aim was to determine the rate and cost of scans being performed for this group of patients.

Method: We utilised a database of prostate cancer patients treated by a radiation oncologist specialising in prostate cancer at the Royal Adelaide Hospital between January 2008 and December 2012. Risk criteria were defined according to the D'Amico system. We identified the staging investigations ordered.

Results: Of 236 consecutive eligible patients, 69 (70%) and 85 (86%) of 99 low risk, and 112 (82%) and 126 (92%) of 137 intermediate-risk patients, were found to have had staging CTAP and WBBS, respectively. In fact, only 9.7% of the patients followed the international best practice guidelines and had no staging investigations. None of these scans showed evidence of metastatic disease. The total costs of these investigations for the low and intermediate-risk groups were approximately AUD 75 000 and AUD 116 000, respectively.

Conclusion: We found that there is clearly a significant overuse of staging investigations for both these groups while the incidence of metastases identified was very low. This is likely to have a significant impact on the waiting time for scans and lead to substantial waste of resources. It places unnecessary financial burden on the patients and the healthcare system. There are also issues of increased radiation and contrast exposure, and potentially unnecessary further investigations.
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http://dx.doi.org/10.1111/1754-9485.12234DOI Listing
February 2015

External evaluation of the Radiation Therapy Oncology Group brachial plexus contouring protocol: several issues identified.

J Med Imaging Radiat Oncol 2014 9;58(3):360-8. Epub 2014 Apr 9.

Alan Walker Cancer Centre, Royal Darwin Hospital, Darwin, Northern Territory, Australia; Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Introduction: The aims of the study were to evaluate interobserver variability in contouring the brachial plexus (BP) using the Radiation Therapy Oncology Group (RTOG)-approved protocol and to analyse BP dosimetries.

Methods: Seven outliners independently contoured the BPs of 15 consecutive patients. Interobserver variability was reviewed qualitatively (visually by using planning axial computed-tomography images and anteroposterior digitally reconstructed radiographs) and quantitatively (by volumetric and statistical analyses). Dose-volume histograms of BPs were calculated and compared.

Results: We found significant interobserver variability among outliners in both qualitative and quantitative analyses. These were most pronounced for the T1 nerve roots on visual inspection and for the BP volume on statistical analysis. The BP volumes were smaller than those described in the RTOG atlas paper, with a mean volume of 20.8 cc (range 11-40.7 cc) compared with 33 ± 4 cc (25.1-39.4 cc). The average values of mean dose, maximum dose, V60Gy, V66Gy and V70Gy for patients treated with conventional radiotherapy and IMRT were 42.2 Gy versus 44.8 Gy, 64.5 Gy versus 68.5 Gy, 6.1% versus 7.6%, 2.9% versus 2.4% and 0.6% versus 0.3%, respectively.

Conclusion: This is the first independent external evaluation of the published protocol. We have identified several issues, including significant interobserver variation. Although radiation oncologists should contour BPs to avoid dose dumping, especially when using IMRT, the RTOG atlas should be used with caution. Because BPs are largely radiologically occult on CT, we propose the term brachial-plexus regions (BPRs) to represent regions where BPs are likely to be present. Consequently, BPRs should in principle be contoured generously.
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http://dx.doi.org/10.1111/1754-9485.12175DOI Listing
April 2015

External validation of the lumbosacral plexus-contouring protocol developed by Yi et al. (IJROBP 2012; 84: 376-82) for pelvic malignancies.

J Med Imaging Radiat Oncol 2014 Feb 29;58(1):117-24. Epub 2013 Aug 29.

Alan Walker Cancer Centre, Royal Darwin Hospital, Darwin, Northern Territory, Australia; Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Purpose: To evaluate interobserver variability in contouring lumbosacral plexuses (LSP) using the protocol developed by Yi et al. (IJROBP 2012; 84: 376-82) and to review LSP dosimetries for conventional radiotherapy and intensity-modulated radiotherapy (IMRT) for pelvic cancers.

Methods And Materials: Using the above-mentioned protocol, seven outliners independently contoured LSPs of 10 consecutive patients (five patients treated with conventional radiotherapy and five with IMRT). Interobserver variability was reviewed visually by using planning axial CT images and anteroposterior digitally reconstructed radiographs. Dosimetries of LSPs were also calculated and compared.

Results: There was a notable learning curve for each outliner; duration to outline the first patient was 45-185 minutes, versus 15-50 minutes after six patients. We found significant interobserver variability among outliners below the level of the S2 nerve roots. The LSP volumes (mean volume range of 40.9-58.4 cc) were smaller than those described in the atlas paper (71-138 cc). The mean values of mean dose, maximum dose, V40 Gy, V50 Gy and V55 Gy, respectively, for patients treated with conventional radiotherapy versus those treated with IMRT were 35.5 Gy versus 33.6 Gy, 52.2 Gy versus 52.2 Gy, 61.3% versus 54.4%, 14.9% versus 18.8% and 0% versus 2.5%.

Conclusion: We conclude that the protocol developed by Yi et al. is a useful set of guidelines but suggest that additional at-risk components of the LSP also be contoured. We recommend that radiation oncologists practise 'nerve-sparing' radiotherapy by contouring LSPs, especially when using IMRT. We propose the term 'lumbosacral plexus regions' (LSPRs) to highlight the fact that LSPs are not always radiologically visible, only the regions where they are likely to be present.
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http://dx.doi.org/10.1111/1754-9485.12106DOI Listing
February 2014

Is "pelvic radiation disease" always the cause of bowel symptoms following prostate cancer intensity-modulated radiotherapy?

Radiother Oncol 2014 Feb 8;110(2):278-83. Epub 2014 Jan 8.

North Coast Cancer Institute, Coffs Harbour, Australia.

Background: Pelvic radiation disease (PRD) also widely known as "radiation proctopathy" is a well recognised late side-effect following conventional prostate radiotherapy. However, endoscopic evaluation and/or specialist referral for new or persistent post-prostate radiotherapy bowel symptoms is not routine and serious diagnoses may potentially be missed. Here we report a policy of endoscopic evaluation of bowel symptoms persisting >90 days post radiotherapy for prostate cancer.

Methods And Materials: A consecutive series of 102 patients who had radical prostate intensity-modulated radiotherapy (IMRT)/image-guided radiotherapy (IGRT) and who had new or ongoing bowel symptoms or positive faecal occult blood tests (FOBT) on follow up visits more than three months after treatment, were referred for endoscopic examination. All but one (99%) had full colonoscopic investigation.

Results: Endoscopic findings included gastric/colonic/rectal polyps (56%), diverticular disease (49%), haemorrhoids (38%), radiation proctopathy (29%), gastritis/oesophagitis (8%) and rarer diagnoses, including bowel cancer which was found in 3%. Only four patients (4%) had radiation proctopathy without associated pathology and 65 patients (63%) had more than one diagnosis. If flexible sigmoidoscopy alone were used, 36.6% of patients and 46.6% patients with polyp(s) would have had their diagnoses missed.

Conclusions: Our study has shown that bowel symptoms following prostate IMRT/IGRT are due to numerous diagnoses other than PRD, including malignancy. Routine referral pathways should be developed for endoscopic evaluation/specialist review for patients with new or persistent bowel symptoms (or positive FOBT) following prostate radiotherapy. This recommendation should be considered for incorporation into national guidelines.
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http://dx.doi.org/10.1016/j.radonc.2013.11.012DOI Listing
February 2014