Adaptive radiotherapy for breast cancer.

Research in the field of local and locoregional breast cancer radiotherapy aims to maintain excellent oncological outcomes while reducing treatment-related toxicity. Adaptive radiotherapy (ART) considers variations in target and organs at risk (OARs) anatomy occurring during the treatment course and integrates these in re-optimized treatment plans. Exploiting ART routinely in clinic may result in smaller target volumes and better OAR sparing, which may lead to reduction of acute as well as late toxicities. In this review MR-guided and CT-guided ART for breast cancer patients according to different clinical scenarios (neoadjuvant and adjuvant partial breast irradiation, whole breast, chest wall and regional nodal irradiation) are reviewed and their advantages as well as challenging aspects discussed.

Cardiac Morbidity Following Chemoradiation in Stage III Non-small Cell Lung Cancer Patients: A Population-Based Cohort Study.

AIMS: To assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. MATERIALS AND METHODS: Patients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. RESULTS: In total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4-22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. CONCLUSION: The risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy.

A Randomised Phase II Clinical Trial Comparing the Deliverability and Acute Toxicity of Wide Tangent versus Volumetric Modulated Arc Therapy to the Breast and Internal Mammary Chain.

AIMS: Inclusion of the internal mammary chain in the radiotherapy target volume (IMC-RT) improves disease-free and overall survival in higher risk breast cancer patients, but increases radiation doses to heart and lungs. Dosimetric data show that either modified wide-tangential fields (WT) or volumetric modulated arc therapy (VMAT) together with [AQ1]voluntary deep inspiration breath hold (vDIBH) keep mean heart doses below 4 Gy in most patients. However, the impact on departmental resources has not yet been documented. This phase II clinical trial compared the time taken to deliver IMC-RT using either WT and vDIBH or VMAT and vDIBH, together with planning time, dosimetry, set-up reproducibility and toxicity. MATERIALS AND METHODS: Left-sided breast cancer patients requiring IMC-RT were randomised to receive either WT(vDIBH) or VMAT radiotherapy. The primary outcome was treatment time, powered to detect a minimum difference of 75 min (5 min/fraction) between techniques. The population mean displacement, systematic error and random error for cone beam computed tomography chest wall matches in three directions of movement were calculated. Target volume and organ at risk doses were compared between groups. Side-effects, including skin (Radiation Therapy Oncology Group), lung and oesophageal toxicity (Common Terminology Criteria for Adverse Events v 4.03) rates, were compared between the groups over 3 months. Patient-reported outcome measures, including shoulder toxicity at baseline, 6 months and 1 year, were compared. RESULTS: Twenty-one patients were recruited from a single UK centre between February 2017 and January 2018. The mean (standard deviation) total treatment time per fraction for VMAT treatments was 13.2 min (1.7 min) compared with 28.1 min (3.3 min) for WT(vDIBH). There were no statistically significant differences in patient set-up errors in between groups. The average mean heart dose for WT(vDIBH) was 2.6 Gy compared with 3.4 Gy for VMAT(vDIBH) (P = 0.13). The mean ipsilateral lung V17Gy was 32.8% in the WT(vDIBH) group versus 34.4% in the VMAT group (P = 0.2). The humeral head (mean dose 16.8 Gy versus 2.8 Gy), oesophagus (maximum dose 37.3 Gy versus 20.1 Gy) and thyroid (mean dose 22.0 Gy versus 11.2 Gy) all received a statistically significantly higher dose in the VMAT group. There were no statistically significant differences in skin, lung or oesophageal toxicity within 3 months of treatment. Patient-reported outcomes of shoulder toxicity, pain, fatigue, breathlessness and breast symptoms were similar between groups at 1 year. CONCLUSION: VMAT(vDIBH) and WT(vDIBH) are feasible options for locoregional breast radiotherapy including the IMC. VMAT improves nodal coverage and delivers treatment more quickly, resulting in less breath holds for the patient. This is at the cost of increased dose to some non-target tissues. The latter does not appear to translate into increased toxicity in this small study.

Hydrogen storage in purified multi-walled carbon nanotubes: gas hydrogenation cycles effect on the adsorption kinetics and their performance.

Multi-walled carbon nanotubes (MWCNTs) are an alternative for storage with low cost, eco-friendly, and good performance for both process adsorption and desorption. Herein, a purification procedure of MWCNTs was successfully described and studied by using XRD, TEM, Raman spectroscopy and by means of N2 adsorption-desorption isotherms using the BET method. The H2 storage properties at room temperature of the purified carbon nanotubes exposed to gas under pressures between 0.39 and 13.33 kPa was investigated by using the quartz crystal microbalance technique. It was found that the H2 adsorption capacity is strongly dependent on the morphological and structural characteristics of the carbon nanotubes and their specific surface area. The best sample with specific surface area of 729.4 ± 3 m2 g-1 shows a maximum adsorption capacity of 3.46 wt% at 12.79 kPa of H2 exposure pressure. The adsorption kinetics (t95%) from the different purified MWCNTs was also investigated as a function of the H2 exposure pressure as well as the performance of these MWCNTs on the reversibility of the H2 loading/unloading process when underwent to successive cycles of gas exposure.

Relationship of Urethral Dose and Genitourinary Toxicity Among Patients Receiving Vaginal High Dose Rate Interstitial Brachytherapy.

AIMS: Interstitial brachytherapy (ISBT) plays an important role in the management of locally advanced gynaecological malignancies. However, the relationship between urinary toxicity and dose to the urethra is not well understood. We sought to evaluate the correlation between urethral dose and the incidence of genitourinary complications among patients undergoing vaginal high dose rate ISBT. MATERIALS AND METHODS: Eighty-three patients treated with ISBT between August 2014 and April 2018 were retrospectively reviewed. CTCAE version 5.0 was used to grade toxicity. Individual treatment plans were evaluated to collect dose parameters. Urethral contours were added to the structure sets using a uniform 1 cm diameter brush and minimum doses to the hottest 0.1, 0.2 and 0.5 cm3 (D0.1cm3, D0.2cm3 and D0.5cm3) of the urethra were obtained. Total (ISBT ± external beam radiotherapy) equivalent doses in 2 Gy fractions (EQD2) received by the targets and organs at risk were calculated. Numerical counts (%) and medians (interquartile range) were used to characterise the data. Fisher's exact and the Mann-Whitney-Wilcox tests were used as appropriate. Receiver operator curve analysis was used to define the urethral threshold dose that correlated to genitourinary toxicity. RESULTS: The median age and follow-up times were 67 years (59-75) and 25 months (16-37), respectively. Patients had predominantly primary endometrial (49%) and vaginal (37%) cancer, with four (5%) patients with metastatic rectal cancer to the vagina. Twenty-four of 79 (30%) patients experienced acute genitourinary toxicity and 34 of 71 (48%) experienced late genitourinary toxicity. In both analyses, the median urethral dose was significantly higher among those with toxicity. Receiver operator curve analysis indicated that D0.1cm3, D0.2cm3 and D0.5cm3 of the urethra were associated with the development of toxicity at doses >78, >71 and >62 Gy, respectively. CONCLUSION: Urethral dose seems to predict genitourinary toxicity in ISBT of vaginal tumours. Further study with an expanded cohort and longer follow-up is warranted.

Patient-reported Quality of Life following Stereotactic Body Radiation Therapy for Primary Kidney Cancer - Results from a Prospective Cohort Study.

AIMS: We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. MATERIALS AND METHODS: Patients were treated on a multi-institutional prospective cohort study with 30-42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. RESULTS: Twenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. CONCLUSIONS: SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.

Chest wall toxicity after stereotactic radiation in early lung cancer: a systematic review.

Background: Radiation-induced chest wall pain (cwp) and rib fracture (rf) are late adverse effects after stereotactic body radiation therapy (sbrt) for stage i non-small-cell lung cancer (nsclc); however, the literature about their incidence and risk factors shows variability. We performed a systematic review to determine the pooled incidence of cwp and rf in the relevant population. Methods: A literature search using the prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines considered English publications in medline and embase from January 1996 to August 2017. Abstracts were screened, followed by full-text review and data extraction. Results: The database searches identified 547 records. Twenty-eight publications comprising 3892 patients met the inclusion criteria. Median reported ages and follow-up durations fell into the ranges 67-82 years and 12-84 months. Prescriptions fell into the range of 40-70 Gy in 3-10 fractions. Despite study heterogeneity, the pooled incidences of cwp and rf were estimated to be 8.94% and 5.27% respectively. Nineteen studies reported cwp grade: 58 of 308 patients (18.8%) experienced grades 3-4 cwp (no grade 5 events reported). Thirteen studies reported rf grade: grades 3-4 rf were observed in 9 of 113 patients (7.96%). A high chest wall V30 was an important predictor of cwp and rf. Conclusions: In patients with stage i nsclc, rates of cwp and rf after sbrt are low; however, tumour location, accurate toxicity reporting, and dose-fractionation schemes might alter those rates. Prospective correlation with dosimetry and quality of life assessment will further improve the understanding of cwp and rf after sbrt.

Incidence of radionecrosis in single-fraction radiosurgery compared with fractionated radiotherapy in the treatment of brain metastasis.

Introduction: Radiation-induced brain necrosis ["radionecrosis" (rn)] is a relatively uncommon but potentially severe adverse effect of stereotactic radiosurgery (srs) for brain metastasis. Although dose, volume, and hypofractionation have been suggested to affect rn rates, patient and treatment variability in this population make it difficult to clearly delineate the risk. We set out to establish the effect of fractionation on rn rates by reviewing patients receiving simultaneous multi-fraction and single-fraction treatment at our centre. Methods: Patients receiving simultaneous (within 1 month) 1-fraction (ssrs) and 3-fraction (fsrs) radiosurgery treatments during 2012-2015 were identified in our institution's database. Serial post-srs magnetic resonance imaging (mri) was reviewed to determine rn and local recurrence. The effect of maximum dose, volume, whole-brain radiotherapy (wbrt), and fractionation on rn development was assessed using logistic regression for paired data. Results are reported using odds ratios (ors) and corresponding 95% confidence intervals (cis). Results: Of 90 patients identified, 22 had at least a 6-month mri follow-up. Median follow-up was 320 days. The most common primary tumour type was non-small-cell lung cancer, followed by breast and rectal cancer. Radionecrosis developed in 16 patients [21 of 62 lesions (34%), with 4 being symptomatic (20%)]. Of the 21 lesions in which rn developed, 11 received 3 fractions, and 10 received 1 fraction. The or for the association between the incidence of rn and maximum dose was 1.0 (95% ci: 0.9 to 1.1); for fractionation it was 1.0 (95% ci: 0.3 to 3.6); for previous wbrt, it was 0.4 (95% ci: 0.2 to 1.2); and for a 10-unit increase in volume, it was 3.1 (95% ci: 1.0 to 9.6). Local recurrence developed in 8 patients (12%), 6 of whom belonged to the ssrs group. Conclusions: Our results indicate that patients receiving srs for multiple brain metastases experience a higher rate of rn than is reported in the literature and poorer survival despite having equivalent local control. Maximum dose did not appear to be associated with rn risk in our cohort, but volume was significantly associated with rn risk. Although fractionated treatment did not directly lower the rate of rn in this population, it might have played a role in reducing the magnitude of the rn risk in large-volume lesions. Further investigation will help to delineate optimal dose and fractionation so as to minimize rn while maintaining local control in this group.

The stability of imaging biomarkers in radiomics: a framework for evaluation.

This paper studies the sensitivity of a range of image texture parameters used in radiomics to: (i) the number of intensity levels, (ii) the method of quantisation to select the intensity levels and (iii) the use of an intensity threshold. 43 commonly used texture features were studied for the gross target volume outlined on the CT component of PET/CT scans of 50 patients with non-small cell lung carcinoma (NSCLC). All cases were quantised for all values between 4 and 128 intensity levels using four commonly used quantisation methods. All results were analysed with and without a threshold range of -200 HU to 300 HU. Cases were ranked for each texture feature and for all quantisation methods with the Spearman's rank correlation coefficient determined to evaluate stability. Results showed large fluctuations in ranking, particularly for low numbers of levels, differences between quantisation methods and with the use of a threshold, with values Spearman's Rank Correlation for many parameters below 0.2. Our results demonstrated the sensitivity of radiomics features to the parameters used during analysis and highlight the risk of low reproducibility comparing studies with slightly different parameters. In terms of the lung cancer CT datasets, this study supports the use of 128 intensity levels, the same uniform quantiser applied to all scans and thresholding of the data. It also supports several of the features recommended in the literature for such studies such as skewness and kurtosis. A recommended framework is presented for curation of the data analysis process to ensure stability of results.

MEDiastinal Irradiation and CArdio-Toxic Effects (MEDICATE): Exploring the Relationship between Cardiac Irradiation and High Sensitivity Troponins.

AIMS: Radiation-induced heart disease is a late effect of cardiac irradiation and has been shown in patients with lymphoma and thoracic cancers. There is no established measurement tool to detect acute cardiac damage. However, high sensitivity troponin I and T (HsTnI and HsTnT) and echocardiograms have shown promise in some studies. A pilot trial was conducted to characterise whether these instruments may detect subclinical radiotherapy-induced cardiac damage. MATERIALS AND METHODS: Eligible patients received high cardiac doses defined by either at least 30 Gy to 5% of cardiac volume or a mean dose of 4 Gy. HsTnI and HsTnT were measured before radiotherapy and after 2 and 4 weeks of radiotherapy; three-dimensional echocardiograms were completed before and 1 year after radiotherapy. RESULTS: Of 19 patients, the median 'mean left ventricular dose' was 3.1 Gy and the 'mean cardiac dose' was 8.6 Gy. Significant positive associations between HsTnI and HsTnT were observed at all time points, but there was no significant association with cardiac dose. The mean left ventricular dose and the maximum left ventricular dose were, however, associated with a decrease in ejection fraction (P = 0.054, 0.043) as well as an increase in left ventricular strain (P = 0.058). CONCLUSION: This study suggests that HsTnI and HsTnT are intimately related, but detection of acute cardiac damage was not shown, potentially due to limitations of these markers or low radiotherapy doses using conformal techniques. Our results also suggest subacute damage at 1 year may depend on the dose to the left ventricle. Further studies are needed, as identification of early damage could facilitate the ability to closely monitor and intervene in patients at risk for radiation-induced heart disease.

Evaluation of a Novel Field-placement Algorithm for Locoregional Breast Cancer Radiotherapy Including the Internal Mammary Chain.

AIMS: Irradiation of the internal mammary chain (IMC) is increasing following recently published data, but the need for formal delineation of lymph node volumes is slowing implementation in some healthcare settings. A field-placement algorithm for irradiating locoregional lymph nodes including the IMC could reduce the resource impact of introducing irradiation of the IMC. This study describes the development and evaluation of such an algorithm. MATERIALS AND METHODS: An algorithm was developed in which six points representing lymph node clinical target volume borders (based on European Society for Radiotherapy and Oncology consensus nodal contouring guidelines) were placed on computed tomography-defined anatomical landmarks and used to place tangential and nodal fields. Single-centre testing in 20 cases assessed the success of the algorithm in covering planning target volumes (PTVs) and adequately sparing organs at risk. Plans derived using the points algorithm were also compared with plans generated following formal delineation of nodal PTVs, using the Wilcoxon signed rank test. Timing data for point placement were collected. Multicentre testing using the same methods was then carried out to establish whether the technique was transferable to other centres. RESULTS: Single-centre testing showed that 95% of cases met the nodal PTV coverage dose constraints (binomial probability confidence interval 75.1-99.9%) with no statistically significant reduction in mean heart dose or ipsilateral lung V17Gy associated with formal nodal delineation. In multicentre testing, 69% of cases met nodal PTV dose constraints and there was a statistically significant difference in IMC PTV coverage using the points algorithm when compared with formally delineated nodal volumes (P < 0.01). However, there was no difference in axillary level 1-4 PTV coverage (P = 0.11) with all cases meeting target volume constraints. CONCLUSIONS: The optimal strategy for breast and locoregional lymph node radiotherapy is target volume delineation. However, use of this novel points-based field-placement algorithm results in dosimetrically acceptable plans without the need for formal lymph node contouring in a single-centre setting and for the breast and level 1-4 axilla in a multicentre setting. Further quality assurance measures are needed to enable implementation of the algorithm for irradiation of the IMC in a multicentre setting.

A Dosimetric Comparison of Breast Radiotherapy Techniques to Treat Locoregional Lymph Nodes Including the Internal Mammary Chain.

AIMS: Radiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs). MATERIALS AND METHODS: In 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance. RESULTS: One hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB). CONCLUSIONS: Simple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics.

Next generation sequencing is informing phenotype: a TP53 example.

The increased availability of next generation sequencing (NGS) and multi gene panel testing has resulted in more frequent TP53 testing of families that do not meet classic testing criteria. We investigated testing criteria, family history and result outcome in a cohort of Irish probands undergoing TP53 full sequencing. All TP53 test requests processed through the national genetic testing laboratory between 2012 and 2014 were retrospectively reviewed. Personal and family cancer histories were collected, including tumour type and age at diagnosis, from two adult cancer genetic services in Ireland. Association between Li Fraumeni syndrome (LFS) or Li Fraumeni like syndrome (LFL) criteria and test result was examined. One hundred and 35 TP53 test requests were identified. Family history data and test results were available on 123 of the TP53 test requests (118 female; 5 male). 59/123 (48%) did not meet classic LFS or LFL criteria. Two individuals from this group harboured pathogenic TP53 mutations, giving a 3% mutation detection rate in those not meeting testing criteria. Both were female and had a personal history of early onset bilateral breast cancer with no reported LFS cancers in the family. 64/123 (52%) met LFS or LFL criteria and were all TP53 negative. 37/64 (57.8%) met Chompret criteria, 19/64 (29.7%) met Eeles and 7/64 (10.9%) met Eeles and Chompret and 1/64 (1.6%) met Classic LFS criteria. Stringent testing criteria miss germline mutations in TP53. Broadening the criteria for TP53 testing may improve our understanding of the phenotype and penetrance in the association syndrome.

Endobronchial brachytherapy for metastasis from extrapulmonary malignancies as an effective treatment for palliation of symptoms.

PURPOSE: Endobronchial metastasis (EBM) originating from primary cancers outside the lung is rare. External beam radiotherapy is often attempted for control of symptoms with variable effectiveness and retreatment is challenging if symptoms recur. There is limited documentation of high-dose-rate brachytherapy for EBM in the literature. METHODS AND MATERIALS: A prospective database was created from 2006 to 2015. Patients with EBM who received high-dose-rate brachytherapy were included. Cough, dyspnea, chest pain, and hemoptysis were assessed and graded (0-4) at the time of initial consult and in followup. Symptom-free survival and re-expansion were assessed. RESULTS: Thirty-five patients with EBM were identified. Most patients received three fractions of 700 cGy, and 17 patients had prior external beam radiotherapy. Median symptom-free and overall survival were 67 and 117 days. After brachytherapy, improvement in cough was documented in 75.0%, hemoptysis in 76.4%, dyspnea in 60.0% for a median of 3-6 months. Of the 22 patients who had subsequent chest imaging, re-expansion was documented in 32%. There were no significant toxicities reported. CONCLUSIONS: Brachytherapy appears effective in achieving durable symptom control of cough hemoptysis, and dyspnea in patients with EBM and should be considered routinely for palliation where available. Further studies are required to better characterize expected symptom improvement, lung re-expansion rates, and efficacy in comparison with other local treatments.

The UK HeartSpare Study (Stage II): Multicentre Evaluation of a Voluntary Breath-hold Technique in Patients Receiving Breast Radiotherapy.

AIMS: To evaluate the feasibility and heart-sparing ability of the voluntary breath-hold (VBH) technique in a multicentre setting. MATERIALS AND METHODS: Patients were recruited from 10 UK centres. Following surgery for early left breast cancer, patients with any heart inside the 50% isodose from a standard free-breathing tangential field treatment plan underwent a second planning computed tomography (CT) scan using the VBH technique. A separate treatment plan was prepared on the VBH CT scan and used for treatment. The mean heart, left anterior descending coronary artery (LAD) and lung doses were calculated. Daily electronic portal imaging (EPI) was carried out and scanning/treatment times were recorded. The primary end point was the percentage of patients achieving a reduction in mean heart dose with VBH. Population systematic (Σ) and random errors (σ) were estimated. Within-patient comparisons between techniques used Wilcoxon signed-rank tests. RESULTS: In total, 101 patients were recruited during 2014. Primary end point data were available for 93 patients, 88 (95%) of whom achieved a reduction in mean heart dose with VBH. Mean cardiac doses (Gy) for free-breathing and VBH techniques, respectively, were: heart 1.8 and 1.1, LAD 12.1 and 5.4, maximum LAD 35.4 and 24.1 (all P<0.001). Population EPI-based displacement data showed Σ =+1.3-1.9 mm and σ=1.4-1.8 mm. Median CT and treatment session times were 21 and 22 min, respectively. CONCLUSIONS: The VBH technique is confirmed as effective in sparing heart tissue and is feasible in a multicentre setting.

The importance of early life in childhood obesity and related diseases: a report from the 2014 Gravida Strategic Summit.

Obesity and its related non-communicable diseases (NCDs), such as type 2 diabetes, heart disease and cancer, impose huge burdens on society, particularly the healthcare system. Until recently, public health and policy were primarily focused on secondary prevention and treatment of NCDs. However, epidemiological and experimental evidence indicates that early-life exposures influence the risk of childhood obesity and related diseases later in life, and has now focused attention on the health of both mother and child. During pregnancy and the early neonatal period, individuals respond to their environment by establishing anatomical, physiological and biochemical trajectories that shape their future health. This period of developmental plasticity provides an early window of opportunity to mitigate the environmental insults that may increase an individual's sensitivity to, or risk of, developing obesity or related diseases later in life. Although much investigation has already occurred in the area of Developmental Origins of Health and Disease research, the science itself is still in its infancy. It remains for researchers to tackle the important outstanding questions and translate their knowledge into workable solutions for the public good. The challenge, however, is to decide which areas to focus on. With these opportunities and challenges in mind, the 2014 Gravida Summit convened to examine how its early-life research program can determine which areas of research into mechanisms, biomarkers and interventions could contribute to the international research strategy to fight childhood obesity and its related diseases.

Extragonadal teratomas of the adult abdomen and pelvis: a pictorial review.

Teratomas comprise a spectrum of tumours that have striking imaging appearances and are commonly considered when evaluating a mass in the female pelvis. A subgroup of these tumours located in an extragonadal abdominopelvic location, in contrast, are extremely rare and can affect both sexes. Extragonadal teratomas can occur at all ages, are particularly unusual in adults and can cause confusion in the differential diagnosis, especially in children. Familiarity with the imaging features of the spectrum of teratomas within the abdominal cavity is therefore of great importance, as radiological diagnosis can guide treatment, prevent delays in diagnosis and avoid sequelae. This article summarizes the radiological appearances of these rare extragonadal tumours in adults in relation to their pathology, malignant potential, location and behaviour. Although uncommon, teratomas should be considered in the differential diagnosis of extragonadal abdominal masses, particularly in young adults.

The effect of image guidance on dose distributions in breast boost radiotherapy.

AIMS: To determine the effect of image-guided radiotherapy on the dose distributions in breast boost treatments. MATERIALS AND METHODS: Computed tomography images from a cohort of 60 patients treated within the IMPORT HIGH trial (CRUK/06/003) were used to create sequential and concomitant boost treatment plans (30 cases each). Two treatment plans were created for each case using tumour bed planning target volume (PTV) margins of 5 mm (achieved with image-guided radiotherapy) and 8 mm (required for bony anatomy verification). Dose data were collected for breast, lung and heart; differences with margin size were tested for statistical significance. RESULTS: A median decrease of 29 cm(3) (range 11-193 cm(3)) of breast tissue receiving 95% of the prescribed dose was observed where image-guided radiotherapy margins were used. Decreases in doses to lungs, contralateral breast and heart were modest, but statistically significant (P < 0.01). Plan quality was compromised with the 8 mm PTV margin in one in eight sequential boost plans and one third of concomitant boost plans. Tumour bed PTV coverage was <95% (>91%) of the prescribed dose in 12 cases; in addition, the required partial breast median dose was exceeded in nine concomitant boost cases by 0.5-3.7 Gy. CONCLUSIONS: The use of image guidance and, hence, a reduced tumour bed PTV margin, in breast boost radiotherapy resulted in a modest reduction in radiation dose to breast, lung and heart tissues. Reduced margins enabled by image guidance were necessary to discriminate between dose levels to multiple PTVs in the concomitant breast boost plans investigated.

Multileaf collimation cardiac shielding in breast radiotherapy: Cardiac doses are reduced, but at what cost?

AIMS: To measure cardiac tissue doses in left-sided breast cancer patients receiving supine tangential field radiotherapy with multileaf collimation (MLC) cardiac shielding of the heart and to assess the effect on target volume coverage. MATERIALS AND METHODS: Sixty-seven consecutive patients who underwent adjuvant radiotherapy to the left breast (n = 48) or chest wall (n = 19) in 2009/2010 were analysed. The heart, left anterior descending coronary artery (LAD), whole breast and partial breast clinical target volumes (WBCTV and PBCTV) were outlined retrospectively (the latter only in patients who had undergone breast-conserving surgery [BCS]). The mean heart and LAD NTDmean and maximum LAD doses (LADmax) were calculated for all patients (NTDmean is a biologically weighted mean dose normalised to 2 Gy fractions using a standard linear quadratic model). Coverage of WBCTV and PBCTV by the 95% isodose was assessed (BCS patients only). RESULTS: The mean heart NTDmean (standard deviation) was 0.8 (0.3) Gy, the mean LAD NTDmean 6.7 (4.3) Gy and the mean LADmax 40.3 (10.1) Gy. Coverage of the WBCTV by 95% isodose was <90% in one in three patients and PBCTV coverage <95% (range 78-94%) in one in 10 BCS patients. CONCLUSION: The use of MLC cardiac shielding reduces doses to cardiac tissues at the expense of target tissue coverage. Formal target volume delineation in combination with an assessment of the likelihood of local relapse is recommended in order to aid decisions regarding field and MLC placement.