Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study.

AIM: This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78. CONCLUSIONS: Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

Examination of the best head tilt angle to reduce the parotid gland dose maintaining a safe level of lens dose in whole-brain radiotherapy using the four-field box technique.

The parotid gland is recognized as a major-risk organ in whole-brain irradiation; however, the beam delivery from the left and right sides cannot reduce the parotid gland dose. The four-field box technique using a head-tilting device has been reported to reduce the parotid gland dose by excluding it from the radiation field. This study aimed to determine the appropriate head tilt angle to reduce the parotid gland dose in the four-field box technique. The bilateral, anterior, and posterior beams were set for each of ten patients. The orbitomeatal plane angle (OMPA) was introduced as an indicator that expresses the head tilt angle. Next, principal component analysis (PCA) was performed to understand the interrelationship between variables (dosimetric parameters of the lens and parotid gland and OMPA). In PCA, the angle between the OMPA vector and maximum lens dose or mean parotid gland dose vector was approximately opposite or close, indicating a negative or positive correlation [r = -0.627 (p < 0.05) or 0.475 (p < 0.05), respectively]. The OMPA that reduced the maximum lens dose to <10 Gy with a 95% confidence interval was approximately 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the OMPA.

Effects of Structural Isomers of Spermine on the Higher-Order Structure of DNA and Gene Expression.

Polyamines are involved in various biological functions, including cell proliferation, differentiation, gene regulation, etc. Recently, it was found that polyamines exhibit biphasic effects on gene expression: promotion and inhibition at low and high concentrations, respectively. Here, we compared the effects of three naturally occurring tetravalent polyamines, spermine (SPM), thermospermine (TSPM), and N4-aminopropylspermidine (BSPD). Based on the single DNA observation with fluorescence microscopy together with measurements by atomic force microscopy revealed that these polyamines induce shrinkage and then compaction of DNA molecules, at low and high concentrations, respectively. We also performed the observation to evaluate the effects of these polyamine isomers on the activity of gene expression by adapting a cell-free luciferase assay. Interestingly, the potency of their effects on the DNA conformation and also on the inhibition of gene expression activity indicates the highest for TSPM among spermine isomers. A numerical evaluation of the strength of the interaction of these polyamines with negatively charged double-strand DNA revealed that this ordering of the potency corresponds to the order of the strength of the attractive interaction between phosphate groups of DNA and positively charged amino groups of the polyamines.

[Development of an In-house Couch Model to Improve Dose Attenuation Correction Accuracy for a Couch with Different Thickness in the Superior-inferior Direction].

As the couch used in external radiation therapy attenuate radiation by interaction, it is necessary to correct attenuation of radiation by inserting a couch model in the treatment planning systems. For a couch whose thickness is different in the superior-inferior direction, it is possible to perform dose calculations with an error within ±1% by using separate different couch models provided by vendors. However, it is difficult to correct attenuation correction accurately with a single couch model. In this study, we created an in-house couch model which can set couch shape and physical density in detail by acquiring CT images of actual couch. When we performed dose calculation by optimizing the physical densities of in-house and vendor couch, it was found that the difference between the measured and the calculated values can be significantly reduced by using in-house couch model. Additionally, by using in-house couch model, it is found that the dose attenuation can be corrected within ±1% for a couch whose thickness is different in the superior-inferior direction.

Trends and distribution of external radiation therapy facilities in Japan based on Survey of Medical Institutions from the Ministry of Health, Labour and Welfare.

This study aimed to explore the distribution of external radiation therapy (RT) facilities, the status of related device installations and the adoption of high-precision RT using Survey of Medical Institutions from the Ministry of Health, Labour and Welfare in Japan. Analysis, categorized by the hospital size and prefecture, provides specific insights into the trends in treatment facility healthcare capabilities. Data on the number of RT facilities, high-precision RT facilities, RT devices and treatment planning systems (TPS) categorized by the number of beds and prefecture from 1996 to 2020 were analyzed. In addition, the study examined the correlation between the high-precision implementation rate and the number of TPSs or radiation oncologists and other medical staff. High-precision RT exceeded 95% in large facilities (800+ beds) but remained <50% in medium-sized facilities (300-499 beds). In a prefecture-by-prefecture analysis, calculation of the maximum-minimum ratio of RT facilities per million population and per 30 km2 revealed a disparity of 3.7 and 73.1 times in the population ratio and the density ratio, respectively. Although a correlation was found between the number of TPSs per RT device or the number of medical physicists per million population and the rate of high-precision RT implementation, no correlation was found among other professions. Detailed analysis based on the hospital size and prefecture provided more specific information on the medical functions of RT facilities in Japan. These findings can potentially contribute to the future development of RT, including the standardization of treatment techniques and optimal resource allocation.

Changing trends in gamma knife surgery to linear accelerator brain stereotactic radiotherapy in Japan: a survey based on the nationwide claims database.

PURPOSE: This study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare. MATERIALS AND METHODS: This study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually. RESULTS: From April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (- 1415 or - 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC. CONCLUSION: The study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

Classification of Patients With Painful Tumors to Predict Response to Palliative Radiation Therapy.

PURPOSE: This study aimed to identify factors affecting pain response to develop a patient classification system for palliative radiation therapy (RT). METHODS AND MATERIALS: Our prospective observational study (UMIN000044984) provided data on patients who received palliative RT for painful tumors. The eligibility criteria were having a numerical rating scale (NRS) score of 2 or more before treatment and receiving palliative RT between August 2021 and September 2022. Post-RT follow-up was scheduled prospectively at 2, 4, 12, 24, 36, and 52 weeks. Pain response was assessed using the International Consensus Pain Response Endpoints criteria, with the primary outcome being the response rate within 12 weeks. Multivariable logistic regression was performed to identify factors affecting pain response and develop the classification system. Each class evaluated the differences in response rate, time to response, and progression. RESULTS: Of the 488 registered lesions, 366 from 261 patients met the criteria. Most patients had bone metastases (75%), of whom 72% were using opioids and 22% underwent reirradiation. Conventional RT (eg, 8-Gy single fraction, 20 Gy in 5 fractions) was administered to 93% of patients. Over a median of 6.8 months of follow-up, the average NRS decreased from 6.1 to 3.4 at 12 weeks for 273 evaluable lesions, with a 60% response rate. Opioid use and reirradiation negatively affected the response rate in multivariate analysis (P < .01). Lesions were categorized into class 1 (no opioid use and no reirradiation; 89 lesions), class 2 (neither class 1 nor 3; 211 lesions), and class 3 (opioid use and reirradiation; 66 lesions), with respective response rates of 75%, 61%, and 36% (P < .001). Time to response was similar across the classes (P = .91), but the progression rates at 24 weeks differed (11%, 27%, and 63%, respectively; P < .001). CONCLUSIONS: Opioid use and reirradiation are factors leading to significant variations in pain response rates and time to progression.

Palliative radiotherapy for painful non-bone lesions in patients with advanced cancer: a single center retrospective study.

PURPOSE: This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. MATERIALS AND METHODS: We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. RESULTS: Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2-4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1-2 adverse events, while none experienced grade 3 or higher toxicity. CONCLUSION: Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Deep Learning-based Lung dose Prediction Using Chest X-ray Images in Non-small Cell Lung Cancer Radiotherapy.

Purpose: This study aimed to develop a deep learning model for the prediction of V20 (the volume of the lung parenchyma that received ≥20 Gy) during intensity-modulated radiation therapy using chest X-ray images. Methods: The study utilized 91 chest X-ray images of patients with lung cancer acquired routinely during the admission workup. The prescription dose for the planning target volume was 60 Gy in 30 fractions. A convolutional neural network-based regression model was developed to predict V20. To evaluate model performance, the coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) were calculated with conducting a four-fold cross-validation method. The patient characteristics of the eligible data were treatment period (2018-2022) and V20 (19.3%; 4.9%-30.7%). Results: The predictive results of the developed model for V20 were 0.16, 5.4%, and 4.5% for the R2, RMSE, and MAE, respectively. The median error was -1.8% (range, -13.0% to 9.2%). The Pearson correlation coefficient between the calculated and predicted V20 values was 0.40. As a binary classifier with V20 <20%, the model showed a sensitivity of 75.0%, specificity of 82.6%, diagnostic accuracy of 80.6%, and area under the receiver operator characteristic curve of 0.79. Conclusions: The proposed deep learning chest X-ray model can predict V20 and play an important role in the early determination of patient treatment strategies.

Estimation of the risk of secondary cancer in rectum and bladder after radiation therapy for prostate cancer using a feasibility dose-volume histogram.

We investigated the risk of secondary cancers in rectum and bladder for prostate cancer radiotherapy using a feasibility assessment tool. We calculated the risk of secondary cancer by generating a dose-volume histogram based on an ideal dose falloff function (f-value). This study found a smaller f-value was associated with a lower secondary cancer risk in the rectum but a higher risk in the bladder. The study suggests setting the f-value at 0-0.1 as the optimization goal for the rectum and 0.4 for the bladder is reasonable and feasible for reducing the risk of secondary cancer and other adverse events.

Dosimetric analysis on computed tomography myelography based treatment planning in stereotactic body radiotherapy for spinal metastases.

This study aimed to quantitatively evaluate the influence of enhanced contrast on the CT myelography image of the spinal cord and/or cauda equina in addition to the target volume in spine SBRT treatment planning. In total, 19 patients who had previously undergone spine SBRT were randomly selected. The rigid image registration accuracy of CT myelography that aligned with the treatment planning CT was evaluated by calculating the normalized mutual information (NMI) and Pearson's correlation coefficient for the vertebral landmarks. At postregistration, the contrast-enhanced region of the CT myelography image was replaced with water-mass density, and the original treatment plan was recalculated on this image. For comparison, the dose was also recalculated on the contrast-enhanced CT myelography images. The NMI and Pearson's correlation coefficients for landmarks were 0.39 ± 0.12 and 0.97 ± 0.04, respectively. The mean D0.035cc of the spinal cord and/or cauda equina on the CT myelography image with the contrast-enhanced region replaced by water-mass density showed -0.37% ± 0.64% changes compared with that of the treatment planning CT. Conversely, the mean D0.035cc in contrast-enhanced CT myelography changed by -1.39% ± 0.51%. The percentage change in D98% for the planning target volume was confirmed to be small by replacing the contrast-enhanced region with water-mass density (p < 0.01). The dose calculation of the target volume, spinal cord, and/or cauda equina using the CT myelography image that replaced the contrast-enhanced region with water-mass density could be a more appropriate procedure with less dose calculation uncertainty.

Development of a device that remotely removes a mask in the head and neck immobilization system: a prototype and demonstration experiment.

In this study, a prototype device was developed to quickly remove the mask used to immobilize the head and neck by remotely releasing the quick fasteners. As a first step in investigating the usefulness of this prototype, we performed repeated removal tests and examined the accuracy of dose calculation. The results showed that the quick-release fasteners of a Type-S system (CIVCO Medical Solutions, Iowa, USA) could be removed remotely and accurately (success rate: 100%). Additionally, the dose errors in treatment planning were negligible (< 1.0%), and the gamma pass rate was equivalent (99.9%). Therefore, this prototype device with a remote system would help manage patient safety in emergencies, such as a disaster or a sudden change in the patient's condition. However, age-related deterioration with long-term clinical use or its ability to link with beam-off still requires further exploration.

Preoperative spirometry and BMI in deep inspiration breath-hold radiotherapy: the early detection of cardiac and lung dose predictors without radiation exposure.

BACKGROUND: This study aimed to investigate preoperative spirometry and BMI as early predictors of the mean heart and lung dose (MHD, MLD) in deep inspiration breath-hold (DIBH) radiotherapy. METHODS: Left-sided breast cancer patients underwent breast-conserving surgery followed by DIBH radiotherapy enrolled. Patients who were not available for preoperative spirometry were excluded. One hundred eligible patients were performed free-breathing (FB-) CT and DIBH-CT for plan comparison. We completed the correlative and multivariate analysis to develop the linear regression models for dose prediction. The residuals were calculated to explore the unpreferable subgroups and compare the prediction accuracy. RESULTS: Among the parameters, vital capacity (VC) and BMI showed the strongest negative correlation with MHD (r = - 0.33) and MLD (r = - 0.34), respectively. They were also significant in multivariate analysis (P < 0.001). Elderly and less VC were independent predictors of increasing absolute residuals (AR). The VC model showed no significant difference in AR compared to the model using the CT parameter of lung volume in FB (LV-FB): median AR of the LV-FB model vs. the VC model was 0.12 vs. 0.11 Gy (P = 0.79). On the other hand, the median AR of the MLD model was 0.38 Gy, showing no specific subgroups of larger AR. CONCLUSION: Preoperative spirometry and BMI are significant predictors of MHD and MLD, respectively. Although elderly and low-VC patients may have larger predictive variations, spirometry might be a substitute for LV-FB as a predictor of MHD.

Parotid gland dose reduction in the hippocampus avoidance whole-brain radiotherapy using helical tomotherapy.

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

Development of deep learning chest X-ray model for cardiac dose prediction in left-sided breast cancer radiotherapy.

Deep inspiration breath-hold (DIBH) is widely used to reduce the cardiac dose in left-sided breast cancer radiotherapy. This study aimed to develop a deep learning chest X-ray model for cardiac dose prediction to select patients with a potentially high risk of cardiac irradiation and need for DIBH radiotherapy. We used 103 pairs of anteroposterior and lateral chest X-ray data of left-sided breast cancer patients (training cohort: n = 59, validation cohort: n = 19, test cohort: n = 25). All patients underwent breast-conserving surgery followed by DIBH radiotherapy: the treatment plan consisted of three-dimensional, two opposing tangential radiation fields. The prescription dose of the planning target volume was 42.56 Gy in 16 fractions. A convolutional neural network-based regression model was developed to predict the mean heart dose (∆MHD) reduction between free-breathing (MHDFB) and DIBH. The model performance is evaluated as a binary classifier by setting the cutoff value of ∆MHD > 1 Gy. The patient characteristics were as follows: the median (IQR) age was 52 (47-61) years, MHDFB was 1.75 (1.14-2.47) Gy, and ∆MHD was 1.00 (0.52-1.64) Gy. The classification performance of the developed model showed a sensitivity of 85.7%, specificity of 90.9%, a positive predictive value of 92.3%, a negative predictive value of 83.3%, and a diagnostic accuracy of 88.0%. The AUC value of the ROC curve was 0.864. The proposed model could predict ∆MHD in breast radiotherapy, suggesting the potential of a classifier in which patients are more desirable for DIBH.

Evaluation of a new acrylic-lead shielding device for peripheral dose reduction during cone-beam computed tomography.

Objective: To clarify the peripheral dose changes, especially in the eye lens and thyroid gland regions, using an acrylic-lead shield in cone-beam computed tomography (CBCT). Methods: The acrylic-lead shield consists of system walls and a system mat. The radiophotoluminescence glass dosemeter was set on the eye lens and thyroid gland regions on the RANDO phantom. The system mat was laid under the RANDO phantom ranging from the top of the head to the shoulders, and then, the system walls shielded the phantom's head. Additionally, the phantom was covered anteriorly with a band that had the same shielding ability as the system mat to cover the thyroid gland region. Protocols for CBCT imaging of the thoracic or pelvic region in clinical practice were used. The measurement was performed with and without the acrylic-lead shield. Results: The dose to the eye lens region was reduced by 45% using the system wall. Conversely, the dose to the thyroid gland was unchanged. The use of the system mat reduced the dose to the thyroid gland region by 47%, and the dose to the eye lens was reduced by 22%. The dose to the eye lens region decreased to the background level using the system walls and mat. Conclusion: The newly proposed device using an acrylic-lead shield reduced the peripheral dose in CBCT imaging. Advances in knowledge: Attention is focused on managing peripheral dose in image-guided radiation therapy. The peripheral dose reduction using the acrylic-lead shield is a new proposal in radiotherapy that has never been studied.

Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays.

Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although -AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than -AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.

Fully automated rigid image registration versus human registration in postoperative spine stereotactic body radiation therapy: a multicenter non-inferiority study.

To confirm the fully automated rigid image registration (A-RIR) accuracy in postoperative spine stereotactic body radiation therapy (SBRT), we conducted a multicenter non-inferiority study compared to the human rigid image registration (H-RIR). Twenty-eight metastatic cancer patients who underwent postoperative spine SBRT are enrolled-image registration (IR) of planning computed tomography (CT) and CT-myelogram for delineating the spinal cord. The adopted A-RIR workflow is a contour-focused algorithm performing a rigid registration by maximizing normalized mutual information (NMI) restricted to the data contained within the automatically extracted contour. Three radiation oncologists (ROs) from multicenters were prompted to review two blinded registrations and choose one for clinical use. Indistinguishable cases were allowed to vote equivalent, counted A-RIR side. A-RIR is considered non-inferior to H-RIR if the lower limit of the 95% confidence interval (CI) of A-RIR preferable/equivalent is greater than 0.45. We also evaluated the NMI improvement from the baseline and the translational/rotational errors between A-RIR and H-RIR. The A-RIR preferable/equivalent was selected in 21 patients (0.75, 95% CI: 0.55-0.89), demonstrating non-inferiority to H-RIR. The A-RIR's NMI improvement was greater than H-RIR in 24 patients: the mean value ± SD was 0.225 ± 0.115 in A-RIR and 0.196 ± 0.114 in H-RIR (P < 0.001). The absolute translational error was 0.38 ± 0.31 mm. The rotational error was -0.03 ± 0.20, 0.05 ± 0.19, -0.04 ± 0.20 degrees in axial, coronal, and sagittal planes (range: -0.66-0.52). In conclusion, A-RIR shows non-inferior to H-RIR in CT and CT-myelogram registration for postoperative spine SBRT planning.