Materials and Methods: Original research studies associating genetic features and normal tissue complications following radiation therapy were identified from PubMed. The distribution of radiogenomic studies was determined by mining the statement of country of origin and racial/ancestrial distribution and the inclusion in analyses. Descriptive analyses were performed to determine the distribution of studies across races/ancestries, countries, and continents and the inclusion in analyses.
Results: Among 174 studies, only 23 with a population of more one race/ancestry which were predominantly conducted in the United States. Across the continents, most studies were performed in Europe (77 studies averaging at 30.6 patients/million population [pt/mil]), North America (46 studies, 20.8 pt/mil), Asia (46 studies, 2.4 pt/mil), South America (3 studies, 0.4 pt/mil), Oceania (2 studies, 2.1 pt/mil), and none from Africa. All 23 studies with more than one race/ancestry considered race/ancestry as a covariate, and three studies showed race/ancestry to be significantly associated with endpoints.
Conclusion: Most toxicity-related radiogenomic studies involved a single race/ancestry. Individual Participant Data meta-analyses or multinational studies need to be encouraged.
MATERIALS AND METHODS: The HVGICs evaluated were Zirconomer [ZR] (Shofu), Equia Forte [EQ] (GC) and Riva [RV] (SDI). Sixty specimens (12mm x 2mm x 2mm) of each material were fabricated using customized Teflon molds. After initial set, the specimens were removed from their molds, finished, measured and randomly divided into 3 groups of 20. Half the specimens in each group were left uncoated while the remaining half was covered with the respective manufacturers' resin coating. The specimens were subsequently conditioned in distilled water, artificial saliva or citric acid at 37°C for 7 days. The uncoated and coated specimens (n=10) were then subjected to dynamic mechanical testing in flexure mode at 37°C with a frequency of 0.1 to 10Hz. Storage modulus, loss modulus and loss tangent data were subjected to normality testing and statistical analysis using one-way ANOVA/Scheffe's post-hoc test and Ttest at significance level p<0.05.
RESULTS: Mean storage modulus ranged from 1.39 ± 0.36 to 10.80 ± 0.86 GPa while mean loss modulus varied from 0.13 ± 0.03 to 0.70 ± 0.14 GPa after conditioning in the different mediums. Values for loss tangent ranged from 39.4 ± 7.75 to 213.2 ± 20.11 (x10 -3 ). Significant differences in visco-elastic properties were observed between mediums and materials. When conditioned in distilled water and artificial saliva,storage modulus was significantly improved when ZR, EQ and RV were uncoated. Significantly higher values were, however, observed with resin coating when the materials were exposed to citric acid.
CONCLUSION: The visco-elastic properties of HVGICs were influenced by both resin coating and chemical environment.
METHODS: PubMed and Scopus electronic databases were searched based on the guidelines established by PRISMA to obtain studies investigating the integration of DTI in intracranial RT/RS treatment planning. References and citations from Google Scholar were also extracted. Eligible studies were extracted for information on changes in dose distribution, treatment parameters, and outcome after DTI integration.
RESULTS: Eighteen studies were selected for inclusion with 406 patients (median study size, 19; range: 2-144). Dose distribution, with or without DTI integration, described changes of treatment parameters, and the reported outcome of treatment were compared in 12, 7, and 10 studies, respectively. Dose distributions after DTI integration improved in all studies. Delivery time or monitor unit was higher after integration. In studies with long-term follow-up (median, >12 months), neurologic deficits were significantly fewer in patients with DTI integration.
CONCLUSIONS: Integrating DTI into RT/RS treatment planning improved dose distribution, with higher treatment delivery time or monitor unit as a potential drawback. Fewer neurologic deficits were found with DTI integration.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition.
RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change.
CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible studies according to PRISMA guidelines. Studies were extracted for information on demographics, DTI changes and associations to cognitive outcomes.
RESULTS: Six studies were selected for inclusion with 110 patients (median study size: 20). 5/6 studies found significant cognitive decline and analysed relationships to DTI changes. Decreased fractional anisotropy (FA) was consistently associated with cognitive decline. Associations clustered at specific regions of cingulum and corpus callosum. Only one study conducted multivariable analysis.
CONCLUSION: Fractional anisotropy is a clinically meaningful biomarker for radiotherapy-related cognitive decline. Studies accruing larger patient cohorts are needed to guide therapeutic changes that can abate the decline.
MATERIALS/METHODS: Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04-RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed.
RESULTS: 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients.
CONCLUSIONS: Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models.
MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates.
RESULTS: A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity.
CONCLUSION: A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.
MATERIALS & METHODS: Data for subdistricts in Malaysia and radiotherapy services were extracted from Department of Statistics Malaysia and Directory of Radiotherapy Centres (DIRAC). Data from DIRAC were validated by direct communication with centres. Locations of radiotherapy centres, distance and travel time to the nearest radiotherapy were estimated using web mapping service, Google Map.
RESULTS: The average distance and travel time from Malaysian population to the closest radiotherapy centre were 82.5km and 83.4mins, respectively. The average distance and travel were not homogenous; East Malaysia (228.1km, 236.1mins), Central (14.4km, 20.1mins), East Coast (124.2km, 108.8mins), Northern (42.9km, 42.8mins) and Southern (36.0km, 39.8mins). The MV/million population for the country is 2.47, East Malaysia (1.76), Central (4.19), East Coast (0.54), Northern (2.40), Southern (2.36). About 25% of the population needs to travel >100 km to get to the closest radiotherapy facility.
CONCLUSION: On average, Malaysians need to travel far and long to reach radiotherapy facilities. The accessibility to radiotherapy facilities is not equitable. The disparity may be reduced by adding centres in East Malaysia and the East Coast.