MRI-guided lung SBRT: Present and future developments

Stereotactic body radiotherapy (SBRT) is rapidly becoming an alternative to surgery for the treatment of early-stage non-small cell lung cancer patients. Lung SBRT is administered in a hypo-fractionated, conformal manner, delivering high doses to the target. To avoid normal-tissue toxicity, it is crucial to limit the exposure of nearby healthy organs-at-risk (OAR).Current image-guided radiotherapy strategies for lung SBRT are mostly based on X-ray imaging modalities. Although still in its infancy, magnetic resonance imaging (MRI) guidance for lung SBRT is not exposure-limited and MRI promises to improve crucial soft-tissue contrast. Looking beyond anatomical imaging, functional MRI is expected to inform treatment decisions and adaptations in the future.This review summarises and discusses how MRI could be advantageous to the different links of the radiotherapy treatment chain for lung SBRT: diagnosis and staging, tumour and OAR delineation, treatment planning, and inter- or intrafractional motion management. Special emphasis is placed on a new generation of hybrid MRI treatment devices and their potential for real-time adaptive radiotherapy.     

Selenium as an adjuvant for modification of radiation response

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.     

Intraoperative radiation therapy in uterine cervical cancer: A review

Locally advanced uterine cervical cancer continues to present a high number of pelvic relapses. Intraoperative radiation therapy (IORT) allows a precise therapeutic intensification in the surgical area in cases in which removal of the tumour recurrence is feasible. At the same time, IORT excludes the radiosensitive organs from the field of irradiation. While the first gynecological IORT took place in 1905, procedures have been limited over the years and the series are retrospective, including few patients. At the same, time recurrences are located at different pelvic areas. Both heterogeneity and the long recruiting time make it difficult to correctly interpret the published results. Despite this, we have reviewed the most relevant publications. Some institutions indicated IORT as a boost on the surgical bed of the excised tumor recurrence. In others, IORT permits an extra radiation dose after radical surgery of the primary tumor, usually in stage IIB. Most studies conclude that the addition of IORT increases the local control but probably with little impact on survival. On the other hand, there is a controversy in the indication of IORT in surgically resectable primary tumours. No clear advantage over the usual scheme of chemoradiation and brachytherapy has been detected. Randomized studies that allow a breakthrough in the conclusions are highly unlikely to be performed in this area.     

Protective effects of activated vitamin D receptor on radiation‐induced intestinal injury

Radiation‐induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) ‐induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti‐injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation‐induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation‐induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation‐induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells.     

Anaplastic thyroid cancer: outcomes of trimodal therapy

BackroundThe purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent.Materials and methodsRetrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes.ResultsSeven patients (4 female) were identified. Median age was 58 years (range 52–83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40–90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66 Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence.ConclusionsDespite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases.     

Proton microbeam radiotherapy with scanned pencil-beams – Monte Carlo simulations

Irradiation, delivered by a synchrotron facility, using a set of highly collimated, narrow and parallel photon beams spaced by 1 mm or less, has been termed Microbeam Radiation Therapy (MRT). The tolerance of healthy tissue after MRT was found to be better than after standard broad X-ray beams, together with a more pronounced response of malignant tissue. The microbeam spacing and transverse peak-to-valley dose ratio (PVDR) are considered to be relevant biological MRT parameters. We investigated the MRT concept for proton microbeams, where we expected different depth-dose profiles and PVDR dependences, resulting in skin sparing and homogeneous dose distributions at larger beam depths, due to differences between interactions of proton and photon beams in tissue. Using the FLUKA Monte Carlo code we simulated PVDR distributions for differently spaced 0.1 mm (sigma) pencil-beams of entrance energies 60, 80, 100 and 120 MeV irradiating a cylindrical water phantom with and without a bone layer, representing human head. We calculated PVDR distributions and evaluated uniformity of target irradiation at distal beam ranges of 60–120 MeV microbeams. We also calculated PVDR distributions for a 60 MeV spread-out Bragg peak microbeam configuration. Application of optimised proton MRT in terms of spot size, pencil-beam distribution, entrance beam energy, multiport irradiation, combined with relevant radiobiological investigations, could pave the way for hypofractionation scenarios where tissue sparing at the entrance, better malignant tissue response and better dose conformity of target volume irradiation could be achieved, compared with present proton beam radiotherapy configurations.     

Determination of optimal planning target volume margins in patients with gynecological cancer

PurposeTo define optimal planning target volume (PTV) margins for intensity modulated radiotherapy (IMRT) ± knee-heel support (KHS) in patients treated with adjuvant radiotherapy.MethodsComputed tomography (CT) scans ± KHS of 10 patients were taken before and at 3rd and 5th week of treatment, fused and compared with initial IMRT plans.ResultsA PTV margin of 15 mm in anteroposterior (AP) and superoinferior (SI) directions and 5 mm in lateral directions were found to be adequate without any difference between ± KHS except for the SI shifts in CTV-primary at the 3rd week. Five mm margin for iliac CTV was found to be inadequate in 10–20% of patients in SI directions however when 7 mm margin was given for iliac PTV, it was found to be adequate. For presacral CTV, it was found that the most striking shift of the target volume was in the direction of AP. KHS caused significantly less volume of rectum and bladder in the treated volume.ConclusionsPTV margin of 15 mm in SI and AP, and 5 mm in lateral directions for CTV-primary were found to be adequate. A minimum of 7 mm PTV margin should be given to iliac CTV. The remarkable shifting in presacral CTV was believed to be due to the unforeseen hip malposition of obese patients. The KHS seems not to provide additional beneficial effect in decreasing the shifts both in CTV-primary and lymphatic, however it may have a beneficial effect of decreasing the OAR volume in PTV margins.     

Monte carlo model and output factors of elekta infinity™ 6 and 10 MV photon beam

AimThis study aimed to commission the Elekta Infinity™ working in 6 and 10 MV photon beam installed in Concord International Hospital, Singapore, and compare the OFs between MC simulation and measurement using PTW semiflex and microDiamond detector for small field sizes.Material and MethodsThere are two main steps in this study: modelling of Linac 6 and 10 MV photon beam and analysis of the output factors for field size 2 × 2–10 × 10 cm². The EGSnrc/BEAMnrc-DOSXYZnrc code was used to model and characterize the Linac and to calculate the dose distributions in a water phantom. The dose distribution and OFs were compared to the measurement data in the same condition.ResultsThe commissioning process was only conducted for a 10 × 10 cm² field size. The PDD obtained from MC simulation showed a good agreement with the measurement. The local dose difference of PDDs was less than 2% for 6 and 10 MV. The initial electron energy was 5.2 and 9.4 MeV for 6 and 10 MV photon beam, respectively. This Linac model can be used for dose calculation in other situations and different field sizes because this Linac has been commissioned and validated using Monte Carlo simulation. The 10 MV Linac produces higher electron contamination than that of 6 MV.ConclusionsThe Linac model in this study was acceptable. The most important result in this work comes from OFs resulted from MC calculation. This value was more significant than the OFs from measurement using semiflex and microDiamond for all beam energy and field sizes because of the CPE phenomenon.     

The influence of temperature on the dynamics of protein precrystallization clusters,studied by photon correlation spectroscopy

Hen-egg white lysozyme was used for studying the influence of temperature on crystallization. The reaction was initiated at variable temperatures, covering the range between 5–50 °C, and was monitored with photon correlation spectroscopy. When aggregation was induced by addition of NaCl, the clusters formed exhibited diffusion limited aggregation behavior and crystals appeared in less than two days. In contrast, (NH₄)₂SO₄ induced aggregation took place mostly in the cross-over regime. In this case, solutions either remained transparent and void of crystals or formed gels within a few weeks. In both cases the kinetics could be dynamically scaled into master curves indicating that the precrystallization formed aggregates are fractals resulting from different collision processes.