Gold nanoparticles (AuNP) can increase the efficacy of radiation therapy by sensitising tumor cells to radiation damage. When used in combination with radiation, AuNPs enhance the rate of cell killing; hence, they may be of great value in radiotherapy. This study assessed the effects of radiation and AuNPs on mitochondrial reactive oxygen species (ROS) generation in cancer cells as an adjunct therapeutic target in addition to the DNA of the cell. Mitochondria are considered one of the primary sources of cellular ROS. High levels of ROS can result in an intracellular state of oxidative stress, leading to permanent cell damage. In this study, human melanoma and prostate cancer cell lines, with and without AuNPs, were irradiated with 6-Megavolt X-rays at doses of 0–8 Gy. Indicators of mitochondrial stress were quantified using two techniques, and were found to be significantly increased by the inclusion of AuNPs in both cell lines. Radiobiological damage to mitochondria was quantified via increased ROS activity. The ROS production by mitochondria in cells was enhanced by the inclusion of AuNPs, peaking at ~4 Gy and then decreasing at higher doses. This increased mitochondrial stress may lead to more effectively kill of AuNP-treated cells, further enhancing the applicability of functionally-guided nanoparticles.

A survey on the patterns of practice of respiratory motion management (MM) was distributed to 111 radiation therapy facilities to inform the development of an end-to-end dosimetry audit including respiratory motion. The survey (distributed via REDCap) asked facilities to provide information specific to the combinations of MM techniques (breath-hold gating – BHG, internal target volume – ITV, free-breathing gating – FBG, mid-ventilation – MidV, tumour tracking – TT), sites treated (thorax, upper abdomen, lower abdomen), and fractionation regimes (conventional, stereotactic ablative body radiation therapy – SABR) used in their clinic. The survey was completed by 78% of facilities, with 98% of respondents indicating that they used at least one form of MM. The ITV approach was common to all MM-users, used for thoracic treatments by 89% of respondents, and upper and lower abdominal treatments by 38%. BHG was the next most prevalent (41% of MM users), with applications in upper abdominal and thoracic treatment sites (28% vs 25% respectively), but minimal use in the lower abdomen (9%). FBG and TT were utilised sparingly (17%, 7% respectively), and MidV was not selected at all. Two distinct treatment workflows (including use of motion limitation, imaging used for motion assessment, dose calculation, and image guidance procedures) were identified for the ITV and BHG MM techniques, to form the basis of the initial audit. Thoracic SABR with the ITV approach was common to nearly all respondents, while upper abdominal SABR using BHG stood out as more technically challenging. Other MM techniques were sparsely used, but may be considered for future audit development.

Adaptive radiotherapy (ART) decision-making benefits from dosimetric information to supplement image inspection when assessing the significance of anatomical changes. This study evaluated a dosimetry-based clinical decision workflow for ART utilizing deformable registration of the original planning computed tomography (CT) image to the daily Cone Beam CT (CBCT) to replace the need for a replan CT for dose estimation. We used 12 retrospective Head & Neck patient cases having a ground truth – a replan CT (rCT) in response to anatomical changes apparent in the daily CBCT – to evaluate the accuracy of dosimetric assessment conducted on synthetic CTs (sCT) generated by deforming the original planning CT Hounsfield Units to the daily CBCT anatomy. The original plan was applied to the sCT and dosimetric accuracy of the sCT was assessed by analyzing plan objectives for targets and organs-at-risk compared to calculations on the ground-truth rCT. Three commercial DIR algorithms were compared. For the best-performing algorithms, the majority of dose metrics calculated on the sCTs differed by less than 4 Gy (5.7% of 70 Gy prescription dose). An uncertainty of ±2.5 Gy (3.6% of 70 Gy prescription) is recommended as a conservative tolerance when evaluating dose metrics on sCTs for head and neck. Synthetic CTs present a valuable addition to the adaptive radiotherapy workflow, and synthetic CT dose estimates can be effectively used in addition to the current practice of visually inspecting the overlay of the planning CT and CBCT to assess the significance of anatomical change.