Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

MRI feature-based radiomics models to predict treatment outcome after stereotactic body radiotherapy for spinal metastases.

OBJECTIVE: This study aimed to extract radiomics features from MRI using machine learning (ML) algorithms and integrate them with clinical features to build response prediction models for patients with spinal metastases undergoing stereotactic body radiotherapy (SBRT). METHODS: Patients with spinal metastases who were treated using SBRT at our hospital between July 2018 and April 2023 were recruited. We assessed their response to treatment using the revised Response Evaluation Criteria in Solid Tumors (version 1.1). The lesions were categorized into progressive disease (PD) and non-PD groups. Radiomics features were extracted from T1-weighted image (T1WI), T2-weighted image (T2WI), and fat-suppression T2WI sequences. Feature selection involved intraclass correlation coefficients, minimal-redundancy-maximal-relevance, and least absolute shrinkage and selection operator methods. Thirteen ML algorithms were employed to construct the radiomics prediction models. Clinical, conventional imaging, and radiomics features were integrated to develop combined models. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, and the clinical value was assessed using decision curve analysis. RESULTS: We included 194 patients with 142 (73.2%) lesions in the non-PD group and 52 (26.8%) in the PD group. Each region of interest generated 2264 features. The clinical model exhibited a moderate predictive value (area under the ROC curve, AUC = 0.733), while the radiomics models demonstrated better performance (AUC = 0.745-0.825). The combined model achieved the best performance (AUC = 0.828). CONCLUSION: The MRI-based radiomics models exhibited valuable predictive capability for treatment outcomes in patients with spinal metastases undergoing SBRT. CRITICAL RELEVANCE STATEMENT: Radiomics prediction models have the potential to contribute to clinical decision-making and improve the prognosis of patients with spinal metastases undergoing SBRT. KEY POINTS: • Stereotactic body radiotherapy effectively delivers high doses of radiation to treat spinal metastases. • Accurate prediction of treatment outcomes has crucial clinical significance. • MRI-based radiomics models demonstrated good performance to predict treatment outcomes.

Comparison between supine and prone patient setup for lumbosacral spinal stereotactic body radiosurgery with CyberKnife.

Objective: The aim of this study is to analyze which tracking modality is more suitable for stereotactic body radiosurgery of lumbosacral spinal tumors by comparing prone and supine patient treatment setup. Methods: Eighteen patients with lumbosacral spinal tumors were selected. CT simulation was performed in the supine position (fixed with a vacuum cushion) and prone position (fixed with a thermoplastic mask and prone plate), respectively. The plans in the supine and prone positions were designed using the xsight spine tracking (XST) and xsight spine prone tracking (XSPT) modalities, respectively. The dose-volume histogram (DVH) parameters, namely, V100%, D95%, Dmean, conformity index (CI), and heterogeneity index (HI) in planning target volume (PTV), as well as Dmax, D0.1cc, D1cc, and D5cc in the cauda equina and bowel were recorded. The supine plans were simulation plans and were not used for treatment, which were only used to record the alignment errors. The spinal tracking correction errors (alignment error) and correlation errors of the synchrony respiratory model in the prone position were recorded during the treatment. After treatment, the simulation plan of the supine position was implemented and the spinal tracking correction errors were recorded. The parameters of correction error and DVH parameters for the two positions were analyzed using the paired t-test to compare the difference in positioning accuracy and dose distribution. In addition, the correlation errors of the synchrony respiratory model in the prone position were analyzed to evaluate the prediction accuracy of the synchrony model. Results: For patient setup, the correction error of the supine position in interior/posterior was (0.18 ± 0.16) mm and the prone position was (0.31 ± 0.26) mm (P< 0.05). The correction error of the supine position in inferior/superior was (0.27 ± 0.24) mm, and the prone position was (0.5 ± 0.4) mm (P< 0.05). The average correlation errors of the synchrony model for left/right, inferior/superior, and anterior/posterior in the prone position were (0.21 ± 0.11) mm, (0.41 ± 0.38) mm, and (0.68 ± 0.42) mm, respectively. For the dose distribution, compared with prone plans, the average CI in supine plans was increased by 4.5% (P< 0.05). There was no significant difference in HI, PTV V100%, D95%, and Dmean between the prone and supine plans. Compared with supine plans, average D1cc and D5cc for the cauda equina was significantly decreased by 4.7 and 15.3% in the prone plan (P< 0.05). For the bowel, average Dmax, D0.1cc, D1cc, and D5cc were reduced by 8.0, 7.7, 5.2, and 26.6% in prone plans (P< 0.05) compared with supine plans. Conclusion: Compared with the supine setup, the prone setup combined with XSPT modality for the lumbosacral spinal stereotactic body radiosurgery can spare the bowel and cauda equina of the middle and low dose irradiation, and decrease the number of beams and monitor units.

Long-term follow-up results of spine tumor treatment using high-dose radiotherapy after 3-dimensional-printed vertebral bodies implantation.

OBJECTIVE: To investigate the long-term safety and efficacy of high-dose radiotherapy after 3D-printed vertebral body implantation in the treatment of spinal tumors. METHODS: Thirty-three participants were recruited between July 2017 and August 2019. 3D-printed vertebral bodies were implanted in each participant, followed by postoperative robotic stereotactic radiosurgery at a dose of 35-40 Gy/5f. The tolerance of the 3D-printed vertebral body and the participant to the high-dose radiotherapy were evaluated. In addition, the local control of tumor and the local progression-free survival of the study participants following 3D-printed vertebral body implantation and high-dose radiotherapy were measured as indexes of effectiveness. RESULTS: Of the 33 participants included in the study, 30, including three participants (10%) with esophagitis of grade 3 or above and two participants (6.7%) with advanced radiation nerve injury, successfully underwent postoperative high-dose radiotherapy. The median follow-up was 26.7 months, and IQR was 15.9 months. Most participants had primary bone tumors with 27 cases (81.8%), and the rest had bone metastases in six cases (18.2%). After high-dose radiotherapy, the 3D-printed vertebrae maintained good vertebral stability and exhibited histocompatibility, without implant fractures. The local control rates were 100%, 88%, and 85% 6 months, 1 year, and 2 years after high-dose radiotherapy, respectively. Tumors recurred in four participants (12.1%) during the follow-up period. The median local progression-free survival after treatment was 25.7 months, with a range of 9.6-33.0 months. CONCLUSION: High-dose radiotherapy for spinal tumors after 3D-printed vertebral body implantation is feasible, elicits low toxicity, and yields satisfactory tumor control.

Predictive model based on DCE-MRI and clinical features for the evaluation of pain response after stereotactic body radiotherapy in patients with spinal metastases.

OBJECTIVE: To investigate the correlation of conventional MRI, DCE-MRI and clinical features with pain response after stereotactic body radiotherapy (SBRT) in patients with spinal metastases and establish a pain response prediction model. METHODS: Patients with spinal metastases who received SBRT in our hospital from July 2018 to April 2022 consecutively were enrolled. All patients underwent conventional MRI and DCE-MRI before treatment. Pain was assessed before treatment and in the third month after treatment, and the patients were divided into pain-response and no-pain-response groups. A multivariate logistic regression model was constructed to obtain the odds ratio and 95% confidence interval (CI) for each variable. C-index was used to evaluate the model's discrimination performance. RESULTS: Overall, 112 independent spinal lesions in 89 patients were included. There were 73 (65.2%) and 39 (34.8%) lesions in the pain-response and no-pain-response groups, respectively. Multivariate analysis showed that the number of treated lesions, pretreatment pain score, Karnofsky performance status score, Bilsky grade, and the DCE-MRI quantitative parameter Ktrans were independent predictors of post-SBRT pain response in patients with spinal metastases. The discrimination performance of the prediction model was good; the C index was 0.806 (95% CI: 0.721-0.891), and the corrected C-index was 0.754. CONCLUSION: Some imaging and clinical features correlated with post-SBRT pain response in patients with spinal metastases. The model based on these characteristics has a good predictive value and can provide valuable information for clinical decision-making. KEY POINTS: • SBRT can accurately irradiate spinal metastases with ablative doses. • Predicting the post-SBRT pain response has important clinical implications. • The prediction models established based on clinical and MRI features have good performance.

Treatment of spinal rhabdomyosarcoma in adults: A case report and literature review of current evidence.

Spinal rhabdomyosarcoma (RMS) is a rare yet highly malignant tumor in adults. Literature on this entity is lacking and no mature treatment guideline is currently available. The treatment arsenals include surgery, radiotherapy and chemotherapy, being used singly or jointly. However, the prognosis is dismal, with a mean overall survival period of 10 months. Thus, any case of this disease with encouraging outcomes shall be shared. A case of a middle-aged female patient with spinal RMS was presented in the current report. The patient suffered from back pain but was neurologically intact. The patient underwent a total en-bloc spondylectomy of the T11-L2 vertebrae and spinal reconstruction with 3D-printed prosthetic vertebrae. Afterwards, the patient received a rigid schedule of stereotactic body radiotherapy (SBRT) and chemotherapy. To date, the patient has survived for 40 months, with the preservation of neurological function and sustained mitigation of local pain after the operation. The patient suffered subcutaneous colonization of tumor cells and pulmonary metastasis 10 months postoperatively, but obtained a long locoregional control of 19 months. In conclusion, total en-bloc lesion resection is indicated for the treatment of isolated, primary spinal RMS in adults. Some authors reported that the usage of new surgical tools and instruments has facilitated surgery, which was previously invasive and technically challenging. Advanced radiotherapy techniques, such as SBRT, which were proven effective for local lesion control, should be implemented early after the operation. Chemotherapy remains the mainstay of treatment, but further research and evidence for the efficacy of regimens specifically for adults are required.

New Staging Model for Radiation-based Hepatocellular Carcinoma Treatment: A National Multicenter Study.

Background and Aims: The study aimed to create a new staging model for radiotherapy-based treatment for prognostic hepatocellular carcinoma (HCC) classification. Methods: The training cohort comprised 658 patients receiving stereotactic body radiotherapy and external validation cohort comprised 533 patients receiving three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. We established a modified staging system as follows: stage I, solitary nodule without macrovascular invasion, or 2-3 nodules no more than 3.0 cm apart, and performance status (PS) 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with any one nodule more than 3.0-cm apart, or ≥4 nodules, and performance status 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion, regional lymph node metastasis or distant metastasis, and performance status 0-2 (IIIa: ALBI-1 grade; IIIb: ALBI-2 grade); stage IV: performance status 3-4, or performance status 0-2 with ALBI-3 grade. We analyzed long-term overall survival based on different stages. Results: The staging model showed an excellent ability to discriminate patients according to four stages and seven substages with notably different curves in the training and validation cohort. The median survival decreased from stages I to IV with 63.0 months in stage I (not reached in Ia, and 53.0 months in Ib), 24.0 months in stage II (28.0 months in IIa, and 22.0 months in IIb), 11.0 months in stage III (18.0 months in IIIa, and 9.0 months in IIIb), and less than 9.0 months in stage IV in the training cohort. Conclusions: The modified staging model may provide an alternative for clinical radiation oncologists.

Surgical Treatment of Spinal Metastatic Pheochromocytoma and Paraganglioma: A Single Institutional Cohort of 18 Patients.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To describe surgeries and treatment outcomes of metastatic pheochromocytomas and paragangliomas (PPGLs) on the spine. METHODS: We reviewed a cohort of 18 patients with spinal PPGLs who were consecutively treated in our spinal center. Their clinical data was reviewed. The survival period and its relevant factors was then analyzed. RESULTS: The cohort included ten cases of pheochromocytomas and eight paragangliomas. The local pain and neurological deficits were the two most common symptoms. One third of the spinal PPGLs were diagnosed as functional tumors, arousing secondary hypertension. The imaging features were consistent with those of osteolytic lesions. The surgical strategies for the cohort included percutaneous vertebroplasty, neurological decompression and partial tumor resection, and total en-bloc resection. The postoperative courses were uneventful except 1 patient developed heart failure. The adjuvant therapies were implemented in 6 patients with 131I-MIBG, five with radiotherapy, two with chemotherapy, and 1 with target therapy. The median survival period was 39 months, and the overall survival rate of 1 year was 77.8% (14/18). The patients' Karnofsky performance scores were positively correlated with the survival period (P < .05). CONCLUSION: Surgery is indicated for intractable local pain and neurological impairment in the patients with spinal PPGLs. Palliative surgical strategies, including neurological decompression and partial tumor resection, could bring fair outcomes, especially for the patients in poor physical conditions.

International consensus on radiotherapy in metastatic non-small cell lung cancer.

Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease. Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide. Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

Effect of stereotactic radiotherapy on immune microenvironment of lung cancer.

Stereotactic radiotherapy (SRT) is one of the main treatment modalities for lung cancer, and the current SRT approach combined with immunotherapy has initially presented good clinical efficacy in lung cancer. SRT activates the immune system through in situ immunization, releasing antigens into the blood, which promotes the antigen-antibody response and then induces tumor cell apoptosis. Dose fractionation has different effects on the immune microenvironment, and the tumor microenvironment after SRT also changes over time, all of which have an impact on SRT combined immunotherapy. Although much research on the immune microenvironment of SRT has been conducted, many problems still require further exploration.

[Expert Consensus on the Treatment of Antiangiogenic Agents for Radiation Brain Necrosis].

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
.

Comparison of Ray Tracing and Monte Carlo Calculation Algorithms for Spine Lesions Treated With CyberKnife.

Purpose: This study attempts to evaluate Ray Tracing (RT) and Monte Carlo (MC) algorithms for CyberKnife treatments of spine lesions and determine whether the MC algorithm is necessary for all spine treatment and compare the RT algorithm and MC algorithm at various spine lesion sites. Methods: The CyberKnife is used for stereotactic body radiotherapy for lesions in the cervical spine (30), thoracic spine (50), lumbar spine (30), and sacral spine (15). Dose was calculated using RT and MC algorithms for patients planned with the same beam angles and monitor units. Dose-volume histograms of the target and selected critical structures are evaluated. Results: The average target coverage of prescribed dose with MC algorithms was 94.80%, 88.47%, 92.52%, and 93.41%, respectively, in cervical, thoracic, lumbar, and sacral spine. For the thoracic spine, the RT algorithm significantly overestimates the percentage volume of the target covered by the prescribed dose, as well as overestimates doses to organs at risk in most cases, including lung, spinal cord, and esophagus. For cervical, lumbar, and sacral spine, the differences of the target coverage of prescription dose were generally less than 3% between the RT and MC algorithms. The differences of doses to organs at risk varied with lesion sites and surrounding organs. Conclusions: In the thoracic spine lesions with beams through air cavities, RT algorithm should be limited and verified with MC algorithm, but the RT algorithm is adequate for treatment of cervical, lumbar, and sacral spine lesions without or with a small amount of beams passing through the lungs.

Two-dimensional speckle tracking echocardiography in evaluating radiation-induced heart damage.

Objective: Radiation-induced heart damage (RIHD) in malignant tumor patients with thoracic radiotherapy has been well documented. However, there is no study on the cardiac toxicity of stereotactic body radiotherapy (SBRT) based on two-dimensional speckle tracking echocardiography (2D STE). Methods: In a prospective cohort trial, 48 patients with malignant tumor (including patients with lung cancer, pulmonary metastases and other tumor) were assigned to receive thoracic SBRT. Circulating biomarkers, electrocardiogram (ECG), echocardiography, and 2D STE were performed prior to and within two months after thoracic radiotherapy. The primary outcome of the trial was a decrease in global longitudinal strain (GLS) ≥ 10%. The secondary outcomes were major adverse cardiovascular events (MACE). Analysis were conducted using paired sample t-test, Wilcoxon signed rank test and Chi square test. Results: The morbidity of RIHD is 44% within 2 months after SBRT in malignant tumor patients. Compared with pre-RT, a significant decrease in GLS was observed post-RT (-17.98 â€‹± â€‹3.54% vs. -16.92 â€‹± â€‹3.41%; P â€‹= â€‹0.008), without any significant change in left ventricular ejection fraction (LVEF) (68.54 â€‹± â€‹6.06 vs. 69.63 â€‹± â€‹4.45; P â€‹= â€‹0.234), left ventricular mass (LVM) (P â€‹= â€‹0.342), ECG parameters, creatine kinase (P â€‹= â€‹0.074), cardiac troponin T (P â€‹= â€‹0.829) or N-terminal pro-B-type natriuretic peptide (P â€‹= â€‹0.453) at during the post-RT period. There was no evidence that RIHD was correlated with age (P â€‹= â€‹1.000), mean heart dose (P â€‹= â€‹0.602), BED (P â€‹= â€‹0.234), EQD2/2 (P â€‹= â€‹0.615), V5 (P â€‹= â€‹0.506), V10 (P â€‹= â€‹0.578), V20 (P â€‹= â€‹0.670) and V30 (P â€‹= â€‹0.741). Subgroup analysis showed, there is still a significant decline of GLS (-18.30 â€‹± â€‹3.79% vs. -17.11 â€‹± â€‹3.58%; P â€‹= â€‹0.018) in patients without anthracycline treatment. And the decrease of GLS (-19.14 â€‹± â€‹2.42% vs. -16.85 â€‹± â€‹2.46%; P â€‹= â€‹0.004) was more significantly post-RT in anthracycline treatment group. MACE were found in one patient over a period of two months after SBRT. Conclusions: By using strain analysis subclinical cardiac dysfunction was found to be evident early after SBRT, despite unchanged conventional indices such as LVEF, ECG parameters or circulating biomarkers. And the decrease of GLS is still existed after the effect of anthracycline was removed. Trial registration: ClinicalTrials.gov, registration number: NCT04443400.

The rationale and toxicity of combined cranial radiotherapy and immune checkpoint inhibitors in non-small cell lung cancer.

Cranial radiation therapy (CRT) remains to be the foundation stone of the management of brain metastases in non-small cell lung cancer (NSCLC). Nevertheless, the care of NSCLC, recently, has been remarkably reshaped by the immune checkpoint inhibitors (ICIs), such as programmed death protein-1 and programmed death ligand-1 inhibitors, which even showed some efficacy in brain metastases. Furthermore, radiotherapy, traditionally regarded as a therapy via localized cytotoxicity, recently was reported to trigger a systemic immune response, thus probably enhancing the antitumor effect of ICIs. Preliminary datasets confirmed that the combination of these two therapies seemed superior to either monotherapy in NSCLC patients with brain metastases with improved efficacy and comparable toxicity. In this review, we started with discussing the rationale for the combination of CRT and ICIs, then outlined the clinical evidence supporting the high safety of this combined therapy, and finally made a preliminary conclusion on the safety of the combination of CRT and ICIs.

Assessment of Delivery Quality Assurance for Stereotactic Radiosurgery With Cyberknife.

PURPOSE: The purpose of this study is to establish and assess a practical delivery quality assurance method for stereotactic radiosurgery with Cyberknife by analyzing the geometric and dosimetric accuracies obtained using a PTW31016 PinPoint ionization chamber and EBT3 films. Moreover, this study also explores the relationship between the parameters of plan complexity, target volume, and deliverability parameters and provides a valuable reference for improving plan optimization and validation. METHODS: One hundred fifty cases of delivery quality assurance plans were performed on Cyberknife to assess point dose and planar dose distribution, respectively, using a PTW31016 PinPoint ionization chamber and Gafchromic EBT3 films. The measured chamber doses were compared with the planned mean doses in the sensitive volume of the chamber, and the measured planar doses were compared with the calculated dose distribution using gamma index analysis. The gamma passing rates were evaluated using the criteria of 3%/1 mm and 2%/2 mm. The statistical significance of the correlations between the complexity metrics, target volume, and the gamma passing rate were analyzed using Spearman's rank correlation coefficient. RESULTS: For point dose comparison, the averaged dose differences (± standard deviations) were 1.6 ± 0.73% for all the cases. For planar dose distribution, the mean gamma passing rate for 3%/1 mm, and 2%/2 mm evaluation criteria were 94.26% ± 1.89%, and 93.86% ± 2.16%, respectively. The gamma passing rates were higher than 90% for all the delivery quality assurance plans with the criteria of 3%/1 mm and 2%/2 mm. The difference in point dose was lowly correlated with volume of PTV, number of beams, and treatment time for 150 DQA plans, and highly correlated with volume of PTV for 18 DQA plans of small target. DQA gamma passing rate (2%/2 mm) was a moderate significant correlation for the number of nodes, number of beams and treatment time, and a low correlation with MU. CONCLUSION: PTW31016 PinPoint ionization chamber and EBT3 film can be used for routine Cyberknife delivery quality assurance. The point dose difference should be within 3%. The gamma passing rate should be higher than 90% for the criteria of 3%/1 mm and 2%/2 mm. In addition, the plan complexity and PTV volume were found to have some influence on the plan deliverability.

Value and significance of brain radiation therapy during first-line EGFR-TKI treatment in lung adenocarcinoma with EGFR sensitive mutation and synchronous brain metastasis: Appropriate timing and technique.

BACKGROUND: For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn-BM), when and how to apply radiotherapy (RT) during first-line tyrosine kinase inhibitor (TKI) treatment remains debatable. METHODS: From a real-world multicenter database, EGFR-mutant patients with syn-BM diagnosed between 2010-2020 and treated with first-line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression-free survival (mIC-PFS), median overall survival (mOS), and their risk factors were estimated. RESULTS: There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC-PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC-PFS in patients ≤60-year-old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first-generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC-PFS and mOS. mIC-PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3-4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third-generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second-line therapy. CONCLUSIONS: Upfront brain RT based on first-line EGFR-TKI might improve IC-PFS but not OS in EGFR-mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.

An Investigation of Non-Coplanar Volumetric Modulated Radiation Therapy for Locally Advanced Unresectable Pancreatic Cancer Using a Trajectory Optimization Method.

PURPOSE: This study was conducted in order to develop a trajectory optimization algorithm for non-coplanar volumetric modulated arc therapy (VMAT) and investigate the potential of organs at risk (OARs) sparing in locally advanced pancreatic cancer patients using non-coplanar VMAT. METHODS AND MATERIALS: Firstly, a cost map that represents the ray-OAR voxel intersections at each source position was generated using a ray-tracing algorithm. A graph search algorithm was then used to determine the least-cost path from the cost map. Lastly, full arcs or partial arcs were selected based on the least-cost path to generate the non-coplanar VMAT (ncVMAT) trajectories. Clinical coplanar VMAT (coVMAT) plans for 11 patients diagnosed with locally advanced unresectable pancreatic cancer (LAPC) receiving 45 to 70 Gy in 25 fractions were replanned using non-coplanar VMAT trajectories. Both coplanar and non-coplanar plans were normalized to cover 95% of the PTV45 Gy volume with a prescription dose of 45 Gy. The conformity index (CI), homogeneity index (HI), PTV coverage, and dose to the OARs were compared between coVMAT and ncVMAT plans. RESULTS: With ncVMAT, the mean coverage of PTV50 Gy, PTV54 Gy, PTV60 Gy, and PTV70 Gy increased significantly. The mean conformity index of PTV45 Gy, PTV54 Gy, and PTV70 Gy was also improved in the ncVMAT plans. Compared with coVMAT plans, the ncVMAT plans resulted in significantly lower doses to the spinal cord, bilateral kidneys, stomach, and duodenum. The maximum dose to the spinal cord decreased by 6.11%. The mean dose to the left and right kidneys decreased by an average of 5.52% and 11.71%, respectively. The D max, D mean, and D 15% of the stomach were reduced by an average of 7.45%, 15.82%, and 16.79%, separately. The D 15% and D mean of the duodenum decreased 6.38% and 5.64%, respectively. CONCLUSION: A trajectory optimization algorithm was developed for non-coplanar VMAT. Compared with conventional coplanar VMAT, non-coplanar VMAT resulted in improved coverage and conformity to the targets. The sparing of OARs was significantly improved in non-coplanar VMAT compared with coVMAT plans for locally advanced pancreatic cancer.

Apatinib plus ifosfamide and etoposide for relapsed or refractory osteosarcoma: A retrospective study in two centres.

For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1-38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7-18.4) months. The median overall survival time was 19.8 (IQR, 13.1-30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials.

Complete remission of metastatic osteosarcoma using combined modality therapy: a retrospective analysis of unselected patients in China.

BACKGROUND: Complete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients. METHODS: We reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy. RESULTS: Eighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4. CONCLUSIONS: Our past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment.