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Refereed/Peer-reviewed Background: Glioblastomas (GBMs) are notorious for their aggressive features, e.g., intrinsic radioresistance, extensive heterogeneity, hypoxia, and highly infiltrative behaviours. The prognosis has remained poor despite recent advances in systemic and modern X-ray radiotherapy. Boron neutron capture therapy (BNCT) represents an alternative radiotherapy technique for GBM. Previously, a Geant4 BNCT modelling framework was developed for a simplified model of GBM. Purpose: The current work expands on the previous model by applying a more realistic in silico GBM model with heterogeneous radiosensitivity and anisotropic microscopic extensions (ME). Methods: Each cell within the GBM model was assigned an (Formula presented.) value associated with different GBM cell lines and a (Formula presented.) B concentration. Dosimetry matrices corresponding to various MEs were calculated and combined to evaluate cell survival fractions (SF) using clinical target volume (CTV) margins of 2.0 & 2.5 cm. SFs for the BNCT simulation were compared with external X-ray radiotherapy (EBRT) SFs. Results: The SFs within the beam region decreased by more than two times compared to EBRT. It was demonstrated that BNCT results in markedly reduced SFs for both CTV margins compared to EBRT. However, the SF reduction as a result of the CTV margin extension using BNCT was significantly lower than using X-ray EBRT for one MEP distribution, while it remained similar for the other two MEP models. Conclusions: Although the efficiency of BNCT in terms of cell kill is superior to EBRT, the extension of the CTV margin by 0.5 cm may not increase the BNCT treatment outcome significantly.

Head and neck squamous cell carcinomas (HNSCC) resulting from human papillomavirus (HPV) are increasing in incidence but demonstrate significantly better treatment response than HNSCC from other causes such as tobacco and alcohol. This study sought to identify differences in HNSCC, intrinsic to HPV status, in their response to radiation dose. Previously unexamined changes in radio-responsiveness following fractionated X-ray irradiation were compared between HPV positive and negative statuses of HNSCC. Six HNSCC cell lines, 3 of each HPV status, were investigated for radiosensitivity by clonogenic assay and modelled by response as a function of dose. Generational cultures of each cell line were developed to follow changes in radiosensitivity after repeated irradiations simulating fractionated radiation therapy. As a group, the HPV positive cell lines were more radiosensitive, but with changes following repeated fractions of dose, and modelling of response as a function of dose, both statuses displayed large radiobiological heterogeneity. These findings challenge current radiobiological assumptions of head and neck cancers as early responding tissue to radiation and may go some way in explaining difficulties reaching consensus in stratification of treatment by HPV status. Consequently, results from this study do not support stratifying radiation therapy by HPV status. Refereed/Peer-reviewed

Introduction: Despite improvements in radiation therapy, chemotherapy and surgical procedures over the last 30 years, pancreatic cancer 5-year survival rate remains at 9%. Reduced stroma permeability and heterogeneous blood supply to the tumour prevent chemoradiation from making a meaningful impact on overall survival. Hypoxia-activated prodrugs are the latest strategy to reintroduce oxygenation to radioresistant cells harbouring in pancreatic cancer. This paper reviews the current status of photon and particle radiation therapy for pancreatic cancer in combination with systemic therapies and hypoxia activators. Methods: The current effectiveness of management of pancreatic cancer was systematically evaluated from MEDLINE® database search in April 2019. Results: Limited published data suggest pancreatic cancer patients undergoing carbon ion therapy and proton therapy achieve a comparable median survival time (25.1 months and 25.6 months, respectively) and 1-year overall survival rate (84% and 77.8%). Inconsistencies in methodology, recording parameters and protocols have prevented the safety and technical aspects of particle therapy to be fully defined yet. Conclusion: There is an increasing requirement to tackle unmet clinical demands of pancreatic cancer, particularly the lack of synergistic therapies in the advancing space of radiation oncology. Refereed/Peer-reviewed

Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 &micro, s produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 &micro, s extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.

Background: Proton radiotherapy produces superior dose distributions compared to photon radiotherapy, reducing side effects. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Our aim was to compare intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) radiation doses for select paediatric intracranial tumours. Methods: IMPT and IMRT dose distributions for gender-matched paediatric cranial CT-datasets (ages 5, 9 and 13 years) were retrospectively calculated to simulate irradiation of supratentorial (ependymoma) and infratentorial (medulloblastoma) target volumes diameters (1&ndash, 3 cm) and position (central and 1&ndash, 2 cm shifts). Results: Clinical dosimetric objectives were achieved for all 216 treatment plans. Whilst infratentorial IMPT plans achieved greater maximum dose sparing to optic structures (4.8&ndash, 12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Mean dose difference for optic chiasm was associated with medulloblastoma target position (p &lt, 0.0197). Supratentorial IMPT plans demonstrated greater dose reduction for the youngest patients (pituitary gland p &lt, 0.001). Conclusions: Normal tissue sparing was achieved regardless of patient age for infratentorial tumours. However, for supratentorial tumours, there was a dosimetric advantage of IMPT across 9 vs. 13-year-old patients.

Licensee MDPI, Basel, Switzerland. It is an agreed fact that overall survival among head and neck cancer patients has increased over the last decade. Several factors however, are still held responsible for treatment failure requiring more in-depth evaluation. Among these, hypoxia and proliferation-specific parameters are the main culprits, along with the more recently researched cancer stem cells. This paper aims to present the latest developments in the field of biomarkers for hypoxia, stemness and tumour proliferation, from an imaging perspective that includes both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) as well as functional magnetic resonance imaging (MRI). Quantitative imaging of biomarkers is a prerequisite for accurate treatment response assessment, bringing us closer to the highly needed personalised therapy. Refereed/Peer-reviewed