Leyla Moghaddasi

Background and PurposeAAPM TG-307 recommends structured validation of electronic portal imaging device (EPID)-based patient-specific quality assurance (PSQA), including independent verification of measured and calculated dose components. This study established and validated a TG-307–aligned commissioning and benchmarking framework for a non-transit EPID-based pre-treatment PSQA system.MethodsFraction Zero Absolute Dose (FZAD) was commissioned on two Varian TrueBeam linacs equipped with aS1000 and aS1200 EPIDs across 6X, 10X, 6FFF and 10FFF energies and two multi-leaf-collimator models. EPID performance was characterised with emphasis on saturation and dose-rate dependence. Independent validation of measured and predicted planar dose components was performed using ion chamber measurements, phantom-based planar, and treatment planning system dose planes in a phantom geometry replicating the EPID configuration. System performance was benchmarked against Portal Dosimetry (PDIP) and phantom-based QA across >800 clinical fields. Error-detection sensitivity was evaluated using receiver operating characteristic (ROC) analysis of externally supplied audit plans.ResultsThe aS1200 panel was linear across all tested dose-rate and source-to-imager distance conditions, whereas the aS1000 required ≥150 cm SID for FFF beams. Independent component validation achieved mean gamma pass rates ≥97% (3%/2 mm). Bland–Altman analysis showed small differences relative to PDIP within narrow 95% limits of agreement. Sensitivity testing demonstrated strong discrimination at 2%/2 mm (area under the ROC curve of 0.886) with improved detection compared to phantom-based QA under stringent specificity constraints.ConclusionA TG-307–aligned framework enables robust, component-level interpretability and actionable insight for tolerance definition and modelling optimisation of EPID-based PSQA implementation.

Background and PurposeAAPM-TG-307 established standardised guidelines for EPID-based patient-specific quality assurance (PSQA), including independent verification of measured and calculated dose components. This study aimed to validate Fraction Zero Absolute Dose (FZAD) within a structured commissioning and benchmarking framework aligned with TG-307.MethodsFZAD was commissioned on two Varian TrueBeam linacs equipped with aS1000 and aS1200 EPIDs for 6X, 10X, 6FFF, and 10FFF beams. EPID performance was characterised with emphasis on saturation and dose-rate dependence. Independent verification of measured (MFZAD) and calculated (DFZAD) planar doses was performed using ion-chamber point measurements, MapCHECK3 planar measurements, and TPS-calculated dose planes. End-to-end validation was conducted on >800 clinical fields and benchmarked against Portal Dosimetry and phantom-based QA. Sensitivity to delivery errors was assessed using externally supplied audit plans.ResultsThe aS1200 panel remained linear across all tested dose-rate and SID combinations, whereas the aS1000 required ≥150 cm SID for FFF beams. Dose-rate dependence was ≤0.5% for both panels. Independent planar verification demonstrated mean gamma pass rates ≥97% under 3%/2mm criteria for both components. End-to-end testing showed consistent trend-based agreement between FZAD and Portal Dosimetry across all energies, particularly for the aS1200 panel. No false-negative outcomes were observed, and the false-positive rate was <3%. Both EPID-based and phantom-based systems detected induced delivery errors, with EPID-based methods more frequently flagging suboptimal plans.ConclusionFZAD performs consistently as an EPID-based pre-treatment PSQA system when commissioned using a component-level framework aligned with TG-307. Independent verification provided insight into system behaviour and informs future optimisation of dose-calculation models.

Glioblastoma (GB), a prevalent and highly malignant primary brain tumour with a very high mortality rate due to its resistance to conventional therapies and invasive nature, resulting in 5-year survival rates of only 4–17%. Despite recent advancements in cancer management, the survival rates for GB patients have not significantly improved over the last 10–20 years. Consequently, there exists a critical unmet need for innovative therapies. One promising approach for GB is Targeted Alpha Therapy (TAT), which aims to selectively deliver potentially therapeutic radiation doses to malignant cells and the tumour microenvironment while minimising radiation exposure to surrounding normal tissue with or without conventional external beam radiation. This approach has shown promise in both pre-clinical and clinical settings. A review was conducted following PRISMA 2020 guidelines across Medline, SCOPUS, and Embase, identifying 34 relevant studies out of 526 initially found. In pre-clinical studies, TAT demonstrated high binding specificity to targeted GB cells, with affinity rates between 60.0% and 84.2%, and minimal binding to non-targeted cells (4.0–5.6%). This specificity significantly enhanced cytotoxic effects and improved biodistribution when delivered intratumorally. Mice treated with TAT showed markedly higher median survival rates compared to control groups. In clinical trials, TAT applied to recurrent GB (rGB) displayed varying success rates in extending overall survival (OS) and progression-free survival. Particularly effective when integrated into treatment regimens for both newly diagnosed and recurrent cases, TAT increased the median OS by 16.1% in newly diagnosed GB and by 36.4% in rGB, compared to current standard therapies. Furthermore, it was generally well tolerated with minimal adverse effects. These findings underscore the potential of TAT as a viable therapeutic option in the management of GB.

Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging.

The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.

Background Superior treatment responses by patients with human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC), compared to patients with HNSCC from other causes, drive biomarker research to optimize treatment. Most HNSCC patients receive radiation therapy delivered as a fractionated course. Changing HPV status in HNSCC from a positive prognostic marker to a predictive one requires biomarkers that capture cellular radiation response to cumulative dose. Methods Nuclear enlargement, γH2AX expression and micronuclei count, were studied in six HNSCC cell lines after 4 Gy fractionated X-irradiation. Results All HNSCC cell lines displayed altered cellular responses, indicating increasing inability to repair radiation damage with subsequent radiation fractions. Increases in nuclear area were significantly greater among HPV positive cell lines (207% and 67% for the HPV positive and HPV negative groups, respectively). Conclusions A different character of DNA repair dysfunction in the HPV positive group suggests greater chromosomal translocation with accumulated radiation dose.