Surface-guided radiotherapy improves rotational accuracy in gynecological cancer patients.

Background: The aim of this study was to determine if rotational uncertainties in gynecological cancer patients can be reduced using surface imaging (SI) compared to aligning three markers on the patient's skin with in-room lasers (marker-laser). Materials and methods: Fifty gynecological cancer patients treated with external-beam radiotherapy were retrospectively analyzed; 25 patients were positioned with marker-laser and 25 patients were positioned with SI. The values of rotational (pitch and roll) deviations of the patient positions between the treatment-planning computed tomography (CT) and online cone-beam computed tomography (CBCT) were collected for both subcohorts and all treatment fractions after performing automatic registration between the two image sets. Statistical analysis of the difference between the two set-up methods was performed using the Mann-Whitney U-test. Results: The median pitch deviation were 1.5° [interquartile range (IQR): 0.6°-2.6°] and 1.1° (IQR: 0.5°-1.9°) for the marker-laser and SI methods, respectively (p < 0.01). The median roll deviation was 0.5° (IQR: 0.2°-0.9°), and 0.7° (IQR: 0.3°-1.2°) for the marker-laser and SI methods, respectively (p < 0.01). Given the shape of the target, pitch deviations had a greater impact on the uncertainty at the periphery of the target and were considered more relevant. Conclusion: By introducing SI as a set-up method in gynecological cancer patients, higher positioning accuracy could be achieved compared with the marker-laser set-up method. This was demonstrated based on residual deviations rather than deviations corrected for by image-guided radiotherapy (IGRT).

Neoadjuvant chemoradiotherapy may increase the risk of severe anastomotic complications after esophagectomy with cervical anastomosis.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) improves long-term survival for patients with esophageal cancer. On the other hand, there are indications that nCRT may increase the risk for postoperative morbidity. The aims of this study were to estimate the radiation exposure to the site of anastomosis on the gastric fundus and to assess whether nCRT affected the incidence or severity of cervical anastomotic complications. METHODS: A retrospective cohort of patients with cancer of the esophagus or gastroesophageal junction, who were reconstructed with cervical anastomosis. The planned radiation dose to the site of the cervical anastomosis on the gastric fundus was estimated for each patient. RESULTS: The analysis of the dose plans showed that 20 out of 22 (93 %) available patients received radiotherapy toward the planned site of the anastomosis in the region of the gastric fundus with doses ranging from 6 to 40 Gy. In the nCRT group, 12 out of 28 patients (43 %) had anastomotic complications compared to 16 out of 42 (38 %) in the non-RT group (p = 0.69). In the nCRT group, 39 % had anastomotic complications that led to a Clavien-Dindo grade of IVa or higher compared to 17 % in the non-RT group (p = 0.03). The OR for Clavien-Dindo grade IVa or worse was 6.0 (95 % CI 1.52-23.50). CONCLUSION: This small retrospective study suggests that nCRT exposes the future anastomotic site to doses of radiation that may impair healing of the subsequent cervical anastomosis. Our data further suggest that nCRT may increase the severity of cervical anastomotic complications, and this hypothesis needs to be tested in a large prospective study.

Contouring practices and artefact management within a synthetic CT-based radiotherapy workflow for the central nervous system.

BACKGROUND: The incorporation of magnetic resonance (MR) imaging in radiotherapy (RT) workflows improves contouring precision, yet it introduces geometrical uncertainties when registered with computed tomography (CT) scans. Synthetic CT (sCT) images could minimize these uncertainties and streamline the RT workflow. This study aims to compare the contouring capabilities of sCT images with conventional CT-based/MR-assisted RT workflows, with an emphasis on managing artefacts caused by surgical fixation devices (SFDs). METHODS: The study comprised a commissioning cohort of 100 patients with cranial tumors treated using a conventional CT-based/MR-assisted RT workflow and a validation cohort of 30 patients with grade IV glioblastomas treated using an MR-only workflow. A CE-marked artificial-intelligence-based sCT product was utilized. The delineation accuracy comparison was performed using dice similarity coefficient (DSC) and average Hausdorff distance (AHD). Artefacts within the commissioning cohort were visually inspected, classified and an estimation of thickness was derived using Hausdorff distance (HD). For the validation cohort, boolean operators were used to extract artefact volumes adjacent to the target and contrasted to the planning treatment volume. RESULTS: The combination of high DSC (0.94) and low AHD (0.04 mm) indicates equal target delineation capacity between sCT images and conventional CT scans. However, the results for organs at risk delineation were less consistent, likely because of voxel size differences between sCT images and CT scans and absence of standardized delineation routines. Artefacts observed in sCT images appeared as enhancements of cranial bone. When close to the target, they could affect its definition. Therefore, in the validation cohort the clinical target volume (CTV) was expanded towards the bone by 3.5 mm, as estimated by HD analysis. Subsequent analysis on cone-beam CT scans showed that the CTV adjustment was enough to provide acceptable target coverage. CONCLUSION: The tested sCT product performed on par with conventional CT in terms of contouring capability. Additionally, this study provides both the first comprehensive classification of metal artefacts on a sCT product and a novel method to assess the clinical impact of artefacts caused by SFDs on target delineation. This methodology encourages similar analysis for other sCT products.

Clinical implementation of a commercial synthetic computed tomography solution for radiotherapy treatment of glioblastoma.

Background and Purpose: Magnetic resonance (MR)-only radiotherapy (RT) workflow eliminates uncertainties due to computed tomography (CT)-MR image registration, by using synthetic CT (sCT) images generated from MR. This study describes the clinical implementation process, from retrospective commissioning to prospective validation stage of a commercial artificial intelligence (AI)-based sCT product. Evaluation of the dosimetric performance of the sCT is presented, with emphasis on the impact of voxel size differences between image modalities. Materials and methods: sCT performance was assessed in glioblastoma RT planning. Dose differences for 30 patients in both commissioning and validation cohorts were calculated at various dose-volume-histogram (DVH) points for target and organs-at-risk (OAR). A gamma analysis was conducted on regridded image plans. Quality assurance (QA) guidelines were established based on commissioning phase results. Results: Mean dose difference to target structures was found to be within ± 0.7 % regardless of image resolution and cohort. OARs' mean dose differences were within ± 1.3 % for plans calculated on regridded images for both cohorts, while differences were higher for plans with original voxel size, reaching up to -4.2 % for chiasma D2% in the commissioning cohort. Gamma passing rates for the brain structure using the criteria 1 %/1mm, 2 %/2mm and 3 %/3mm were 93.6 %/99.8 %/100 % and 96.6 %/99.9 %/100 % for commissioning and validation cohorts, respectively. Conclusions: Dosimetric outcomes in both commissioning and validation stages confirmed sCT's equivalence to CT. The large patient cohort in this study aided in establishing a robust QA program for the MR-only workflow, now applied in glioblastoma RT at our center.

Effects of redox modulation by inhibition of thioredoxin reductase on radiosensitivity and gene expression.

The thioredoxin system is a promising target when aiming to overcome the problem of clinical radiation resistance. Altered cellular redox status and redox sensitive thiols contributing to induction of resistance strongly connect the ubiquitous redox enzyme thioredoxin reductase (TrxR) to the cellular response to ionizing radiation. To further investigate possible strategies in combating clinical radiation resistance, human radio-resistant lung cancer cells were subjected to a combination of single fractions of γ-radiation at clinically relevant doses and non-toxic levels of a well-characterized thioredoxin reductase inhibitor, the phosphine gold(I) compound [Au(SCN)(PEt(3))]. The combination of the TrxR-inhibitor and ionizing radiation reduced the surviving fractions and impaired the ability of the U1810 cells to repopulate by approximately 50%. In addition, inhibition of thioredoxin reductase caused changes in the cell cycle distribution, suggesting a disturbance of the mitotic process. Global gene expression analysis also revealed clustered genetic expression changes connected to several major cellular pathways such as cell cycle, cellular response to stress and DNA damage. Specific TrxR-inhibition as a factor behind the achieved results was confirmed by correlation of gene expression patterns between gold and siRNA treatment. These results clearly demonstrate TrxR as an important factor conferring resistance to irradiation and the use of [Au(SCN)(PEt(3))] as a promising radiosensitizing agent.

Evaluation of Whole Brain Radiotherapy among Lung Cancer Patients with Brain Metastases in Relation to Health Care Level and Survival.

Whole-brain radiotherapy (WBRT) as a treatment for brain metastases has been questioned over the last years. This study aimed to evaluate health care levels and survival after WBRT in a cohort of lung cancer patients with brain metastases receiving WBRT in Stockholm, Sweden, from 2008 to 2019 (n = 384). If the patients were able to come home again was estimated using logistic regression and odds ratios (OR) and survival by using Cox regression. The median age in the cohort was 65.6 years, the median survival following WBRT was 2.4 months (interquartile range (IQR) 1.2-6.2 months), and 84 (22%) patients were not able to come home after treatment. Significantly more males could come home again after WBRT compared to women (OR = 0.37, 95%CI 0.20-0.68). Patients with performance status scores WHO 3-4 had a median survival of 1.0 months, hazard ratio (HR) = 4.69 (95%CI 3.31-6.64) versus WHO score 0-1. Patients admitted to a palliative ward before WBRT had a median survival of 0.85 months, HR = 2.26 (95%CI 1.53-3.34) versus being at home. In conclusion, patients treated with WBRT had a short median survival and 20% could not be discharged from the hospital following treatment. Significantly more women did not come home again.

Evaluation of setup accuracy for NSCLC patients; studying the impact of different types of cone-beam CT matches based on whole thorax, columna vertebralis, and GTV.

PURPOSE: The aim of this study is to evaluate the patient setup accuracy by investigating the impact of different types of CBCT matches, performed with 3 (translations only) or 6 (including rotations) degrees-of-freedom (DOF). The purpose is also to calculate and compare CTV to PTV margins based on the various CBCT matches, setups using 2D kV planar imaging or setups using skin markers only (non-IGRT). MATERIAL AND METHODS: Setup images from 16 NSCLC patients with weekly CBCT and daily 2D kV planar imaging were analyzed retrospectively. The CBCT matches were based on the columna vertebralis (CV), the whole thorax (WT) and the soft tissue (ST) delineated GTV, where the ST match was chosen as reference. Thus the translational and rotational shifts in three dimensions were assessed. Finally, setup margins were calculated using van Herk's margin recipe. RESULTS: For 80% of the investigated 3 DOF/2D kV CV setups, the translational shifts were within [-3, 2] mm for all three directions. Corresponding values for the 6 DOF/non-IGRT CV and the 6 DOF/non-IGRT ST matches were [-5, 8] mm. Furthermore, 80% of all setups were within ± 2° for pitch-, roll- and yaw-rotations, and none exceeded 5°. The calculated margins for non-IGRT, about 10 mm, were reduced to approximately 4 mm, regardless of using IGRT setup by CBCT or 2D kV imaging on CV. However, if using WT CBCT setup, the margin in LNG direction was slightly larger, approximately 6 mm. CONCLUSION: IGRT for NSCLC is an essential tool for margin reduction, since patient setups based on IGRT leads to approximately half the margin sizes compared to non-IGRT setups. Both CBCT and 2D kV planar imaging yields approximately the same margins for CV/ST matches. The magnitudes of the patient rotations were <5°.

Comparison of predicted and clinical response to radiotherapy: a radiobiology modelling study.

INTRODUCTION: A model to predict clinical outcome after radiation therapy would be a valuable aid in the effort of developing more tailored treatment regimes for different patients. In this work we evaluate the clinical utility of a model that incorporates the following individually measured radiobiology parameters: intrinsic radiosensitivity, proliferation and number of clonogenic cells. The hypothesis underlying the study was that the incorporation of individually measured tumour parameters in a model would increase its reliability in predicting treatment outcome compared with the use of average population derived data. MATERIAL AND METHODS: Forty-six patients with head and neck tumours were analyzed, the majority of whom received both external beam radiotherapy and brachytherapy. Eighteen patients received external beam treatment alone and statistical analyses were carried out on this subgroup. RESULTS: Four of the 18 patients had a >95% calculated probability of cure and none developed a local recurrence resulting in a negative predictive value of 100% (compared with 67% for population-derived data). The sensitivity of the model in predicting local recurrence was 75% (compared with 38% for population-derived data). Using a model that incorporated individually measured radiobiology data, there was a statistically significant difference in local control levels for patients with >95% and <5% predicted probability of local control (chi(2), p = 0.04). DISCUSSION: This study suggests, therefore, that incorporation of measured biological data within a radiobiological model improves its ability to predict radiation therapy outcome compared with the use of population-derived data.

Tissue polypeptide antigen (TPA), hyaluronan and CA 125 as serum markers in malignant mesothelioma.

Mesothelioma is a rare disease with poor prognosis. Monitoring the effect of treatment is a problem and a serum marker might be of use for this purpose. We have studied three serum markers TPA, Hyaluronan and CA 125 in a limited material (11 patients) with the purpose of finding out if they might reflect treatment effect and/or indicate prognosis. The results in our material show that correspondence between initial TPA levels and survival seems to be better than corresponding data regarding Hyaluronan and CAI 25. Five patients show increasing serum levels of all three serum markers from first to last sample as the mesothelioma progressed according to consecutive CT scans. In three of these patients stable disease was followed by a decrease in the serum marker levels. Our results indicate that these three serum markers and mainly TPA might be useful as markers of disease progression and TPA for prediction of survival.

Fractionated irradiation of five human lung cancer cell lines and prediction of survival according to a radiobiology model.

BACKGROUND: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10 × 1 Gy, 5 × 2 Gy or 2 × 5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. RESULTS AND DISCUSSION: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.