Background Recent evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as this results in better neurocognitive preservation compared to whole brain radiotherapy. However, there is often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, delivers a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrated boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes. This technique is abbreviated to HA-SIB-WBRT or HA-WBRT+SIB. Methods We hypothesise that the SIB in HA-SIB-WBRT (experimental arm) will result in better tumour control compared to HA-WBRT (control arm). This may also lead to better intracranial disease control as well as functional and survival outcomes. We aim to conduct a prospective randomised phase II trial in patients who have good performance status, multiple brain metastases (4–25 lesions) and a reasonable life expectancy (> 6 months). These patients will be stratified according to the number of brain metastases and randomised between the 2 arms. We aim for a recruitment of 100 patients from a single centre over a period of 2 years. Our primary endpoint is target lesion control. These patients will be followed up over the following year and data on imaging, toxicity, quality of life, activities of daily living and cognitive measurements will be collected at set time points. The results will then be compared across the 2 arms and analysed. Discussion Patients with brain metastases are living longer. Maintaining functional independence and intracranial disease control is thus increasingly important. Improving radiotherapy treatment techniques could provide better control and survival outcomes whilst maintaining quality of life, cognition and functional capacity. This trial will assess the benefits and possible toxicities of giving a SIB to HA-WBRT. Trial registration Clinicaltrials.gov identifier: NCT04452084. Date of registration 30th June 2020.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

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Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications.

BACKGROUND Recently Hippocampal Avoidance (HA-) WBRT has become a recommended treatment option in patients with multiple (≥ 5) brain metastases and good prognosis. We wanted to investigate the dosimetric feasibility of dose painting technique combining HA-WBRT with a simultaneous integrated boost (SIB) to tumours. METHOD 5 patients who had a CT simulation fused with brain MRI with fine cuts, were selected for this study. Volumes were contoured on T1w contrast images. Whole brain prescription dose was 30Gy in 12 fractions. A PTV margin of 2mm was applied to lesions, except when these were ≤5mm from organs at risks (OARs). A simultaneous integrated boost (SIB) of 48Gy and 40.2Gy was prescribed to these volumes respectively. Hippocampal constraints followed RTOG 0933 protocol. For lesions ≤5mm from OARs, the acceptable D0.03cc≤42Gy was allowed. All plans were planned on EclipseTM v.13.6 TPS using 6MV photons, VMAT technique with 3 coplanar and 1 non-coplanar arcs for Varian TrueBeam machine. RESULTS Plans had between 6–24 lesions with GTV and PTV of 3.02–11.32cc and 7.05–31.74cc respectively. 3 of the plans had lesions within/adjacent to brainstem or hippocampus. The achieved PTV_40.2Gy D95% 37.42–39.05Gy with Conformity Index (CI)(95%) 0.63–1.06, PTV_48Gy D95% 44.64–47.04Gy with CI(95%) 0.75–0.97 and GTV_48Gy D95% 47.44–50.16Gy. Whole brain Dmean 31.87–33.15Gy with a Homogeneity Index (D2%-D98%/Dmean) 0.18–0.58. Hippocampal D100% 8.69–10.1Gy, D0.03cc 16.5–40.43Gy and Dmean 12.66–24.68Gy. SUMMARY: There was a steep learning curve when adopting this technique and multiple plan iterations were made to achieve target constraints. To meet acceptable OAR constraints, SIB coverage was compromised. Lesions ≤5mm from hippocampus resulted in higher Hippocampal average Dmean 22.8Gy vs. 12.8Gy. The significance of this value should be tested in clinical trials. Overall, HA-SIB-WBRT seems feasible even with ≥ 5 brain metastases and could result in better brain metastases control then HA-WBRT alone.