Effective method to reduce the normal brain dose in single-isocenter hypofractionated stereotactic radiotherapy for multiple brain metastases.

BACKGROUND AND PURPOSE: Island blocking and dose leakage problems will lead to unnecessary irradiation to normal brain tissue (NBT) in hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BM) with single-isocenter volumetric modulated arc therapy (VMAT). The present study aimed at investigating whether reducing the number of metastases irradiated by each arc beam could minimize these two problems. MATERIALS AND METHODS: A total of 32 non-small-cell lung cancer (NSCLC) patients with multiple BM received HSRT (24-36 Gy/3 fractions) with single-isocenter VMAT, where each arc beam only irradiated partial metastases (pm-VMAT), were enrolled in this retrospective study. Conventional single-isocenter VMAT plans, where each arc beam irradiated whole metastases (wm-VMAT), was regenerated and compared with pm-VMAT plans. Furthermore, the clinical efficacy and toxicities were evaluated. RESULTS: Pm-VMAT achieved similar target coverage as that with wm-VMAT, with better dose fall-off (P < 0.001) and NBT sparing (P < 0.001). However, pm-VMAT resulted in more monitor units (MU) and longer beam-on time (P < 0.001). The intracranial objective response rate and disease control rate for all patients were 75% and 100%, respectively. The local control rates at 1 year and 2 year were 96.2% and 60.2%, respectively. The median progression-free survival and overall survival were 10.3 months (95% confidence interval [CI] 6.8-13.2) and 18.5 months (95% CI 15.9-20.1), respectively. All treatment-related adverse events were grade 1 or 2, and 3 lesions (2.31%) from 2 patients (6.25%) demonstrated radiation necrosis after HSRT. CONCLUSION: HSRT with pm-VMAT is effective and has limited toxicities for NSCLC patients with multiple BM. Pm-VMAT could provide better NBT sparing while maintaining target dose coverage.

[Two-Dimensional Electron Beam Radiotherapy Planning System with Modeling Function].

In order to adapt to different target shapes and protect the surrounding normal tissues, the design of two-dimensional electron beam radiotherapy planning requires additional lead blocks. But the Pinnacle treatment planning system can not directly shape the lead block conformity to the size of the beam field given by the doctor. Every time, physicists need to manually drag the lead block to form the required beam field. When meeting a two-dimensional electron beam treatment planning with the same field parameters as before, physicists need to rearrange the field for dose calculation, which greatly reduces the design efficiency of the two-dimensional electron beam treatment planning. In this study, we independently developed a two-dimensional electron beam radiotherapy planning system based on Qt Creator. The system can quickly design a two-dimensional electron beam radiotherapy plan, which reduces the repeated work of physicists.

A good response to anti-PD-1 monoclonal antibody plus SBRT in a patient with PD-L1-negative recurrent advanced esophageal cancer: a long-term follow-up case report of a possible abscopal effect.

There are limited treatment options for recurrent advanced esophageal squamous cell carcinoma. A good response with a possible abscopal effect was observed in a patient with programmed death-ligand 1 (PD-L1)-negative recurrent advanced esophageal squamous cell carcinoma treated with an anti-PD-1 monoclonal antibody plus stereotactic body radiotherapy (SBRT). A 66-year-old male patient was diagnosed with recurrent advanced esophageal squamous cell carcinoma with multiple lung metastases (13 metastatic nodules in total) four months after completing radical radiotherapy plus concurrent and consolidated chemotherapy, and PD-L1 expression in the primary esophageal tumor was negative. This patient received 25 cycles of camrelizumab (an anti-PD-1 monoclonal antibody) in total plus upfront SBRT for two metastatic nodules, which was administered after the first cycle of camrelizumab. After this combined treatment, for most nontarget nodules, an obvious volume decrease and fuzzy change were observed, including two nodules that completely vanished. At the end of follow-up, the progression-free survival and duration of response of this patient were 34 months and 32 months, respectively. This case report indicated that an anti-PD-1 monoclonal antibody combined with SBRT was a promising therapeutic strategy for recurrent esophageal squamous cell carcinoma even in patients with negative PD-L1 expression.

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor-mutated non-small-cell lung cancer patients with brain metastases.

BACKGROUND: For epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients with limited brain metastases (BMs), who eventually receive both tyrosine kinase inhibitors (TKIs) treatment and brain radiotherapy, the optimal timing of radiotherapy is not clear. The present retrospective analysis aimed to partly solve this problem. METHODS: In total 84 EGFR-mutated NSCLC patients with limited BMs, who received both TKI treatment and brain hypofractionated stereotactic radiotherapy (HSRT), were enrolled. Patients were divided into three groups based on whether the HSRT was administrated 2 weeks before or after the beginning of TKI treatment (upfront HSRT), when intracranial lesions stabilized after TKI treatment (consolidative HSRT), or when the intracranial disease progressed after TKI treatment (salvage HSRT). The clinical efficacy and toxicities were evaluated. RESULTS: The median intracranial progression-free survival (iPFS) and overall PFS calculated from the initiation of HSRT (iPFS1 and PFS1) of all patients were 17.5 and 13.1 months, respectively. The median iPFS and PFS calculated from the initiation of TKI treatment (iPFS2 and PFS2) of all patients were 24.1 and 18.4 months, respectively. Compared to consolidative and salvage HSRT, upfront HSRT improved iPFS1 (not reached vs. 17.5 months vs. 11.0 months, p < 0.001) and PFS1 (18.4 months vs. 9.1 months vs. 7.9 months, p < 0.001), and reduced the initial intracranial failure rate (12.5% vs. 48.1% vs. 56%, p < 0.001). However, there were no significant differences between the three groups for iPFS2, PFS2, and overall survival. Hepatic metastases and diagnosis-specific Graded Prognostic Assessment (ds-GPA) at 2-3 were poor prognostic factors. CONCLUSION: For patients who receive both TKI treatment and brain HSRT, the timing of HSRT does not seem to influence the eventual therapeutic effect. Further validation in prospective clinical studies is needed.

Going from 3D/3D to 2D/3D registration for noncoplanar setup verification in intracranial single-isocenter multiple-target hypofractionated stereotactic radiotherapy: comparison between kilo-voltage/mega-voltage image pairs and noncoplanar cone-beam computed tomography.

Background: Single-isocenter (SI) noncoplanar volumetric modulated arc therapy (NC-VMAT) has been widely used in stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BMs). However, it is critical to verify patient positioning at a noncoplanar couch angle. This study aimed to compare the noncoplanar setup discrepancies between kilo-voltage/mega-voltage image (kV/MV) orthogonal image pairs with a 2-dimensional/3-dimensional (2D/3D) matching mode and noncoplanar cone-beam computed tomography (NC-CBCT) with a 3D/3D matching mode in SI NC-VMAT HSRT for multiple BMs. Methods: Twenty patients with multiple BMs [2-5] who underwent SI NC-VMAT HSRT were enrolled in this study. Prior to each noncoplanar field delivery, both kV/MV orthogonal image pairs and NC-CBCT were used to determine setup errors. The setup error values reported by NC-CBCT were defined as the gold standard and compared to those reported by kV/MV orthogonal image pairs. The Bland-Altman analysis method was utilized to assess the agreement of the two positioning modalities. Results: In total, 104 kV/MV image pairs and NC-CBCT scans were acquired. The mean setup error differences (SEDs; absolute values) between the two positioning systems were 0.17 mm, 0.21 mm, 0.16 mm, 0.22°, 0.18°, and 0.17° in the vertical, longitudinal, lateral, yaw, pitch, and roll directions, respectively. The maximum SEDs regarding translation and rotation occurred in the longitudinal and yaw directions at 0.60 mm and 0.8°, respectively. Bland-Altman analysis showed excellent agreement between the two positioning modalities, and the 95% limits of agreement (LOAs) never exceeded 0.6 mm and 0.6° in the translational and rotational directions, respectively. Only 4.80% of SEDs exceeded the tolerance of 0.5 mm/0.5°. Conclusions: Orthogonal kV/MV image pairs with 2D/3D matching mode could provide comparable accuracy for noncoplanar positioning as NC-CBCT with 3D/3D matching mode.

Radiomics analysis of EPID measurements for patient positioning error detection in thyroid associated ophthalmopathy radiotherapy.

PURPOSE: Electronic portal imaging detector (EPID)-based patient positioning verification is an important component of safe radiotherapy treatment delivery. In computer simulation studies, learning-based approaches have proven to be superior to conventional gamma analysis in the detection of positioning errors. To approximate a clinical scenario, the detectability of positioning errors via EPID measurements was assessed using radiomics analysis for patients with thyroid-associated ophthalmopathy. METHODS: Treatment plans of 40 patients with thyroid-associated ophthalmopathy were delivered to a solid anthropomorphic head phantom. To simulate positioning errors, combinations of 0-, 2-, and 4-mm translation errors in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were introduced to the phantom. The positioning errors-induced dose differences between measured portal dose images were used to predict the magnitude and direction of positioning errors. The detectability of positioning errors was assessed via radiomics analysis of the dose differences. Three classification models-support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost-were used for the detection of positioning errors (positioning errors larger or smaller than 3 mm in an arbitrary direction) and direction classification (positioning errors larger or smaller than 3 mm in a specific direction). The receiver operating characteristic curve and the area under the ROC curve (AUC) were used to evaluate the performance of classification models. RESULTS: For the detection of positioning errors, the AUC values of SVM, KNN, and XGBoost models were all above 0.90. For LR, SI, and AP direction classification, the highest AUC values were 0.76, 0.91, and 0.80, respectively. CONCLUSIONS: Combined radiomics and machine learning approaches are capable of detecting the magnitude and direction of positioning errors from EPID measurements. This study is a further step toward machine learning-based positioning error detection during treatment delivery with EPID measurements.

Low-dose cone-beam CT (LD-CBCT) reconstruction for image-guided radiation therapy (IGRT) by three-dimensional dual-dictionary learning.

BACKGROUND: To develop a low-dose cone beam CT (LD-CBCT) reconstruction method named simultaneous algebraic reconstruction technique and dual-dictionary learning (SART-DDL) joint algorithm for image guided radiation therapy (IGRT) and evaluate its imaging quality and clinical application ability. METHODS: In this retrospective study, 62 CBCT image sets from February 2018 to July 2018 at west china hospital were randomly collected from 42 head and neck patients (mean [standard deviation] age, 49.7 [11.4] years, 12 females and 30 males). All image sets were retrospectively reconstructed by SART-DDL (resultant D-CBCT image sets) with 18% less clinical raw projections. Reconstruction quality was evaluated by quantitative parameters compared with SART and Total Variation minimization (SART-TV) joint reconstruction algorithm with paired t test. Five-grade subjective grading evaluations were done by two oncologists in a blind manner compared with clinically used Feldkamp-Davis-Kress algorithm CBCT images (resultant F-CBCT image sets) and the grading results were compared by paired Wilcoxon rank test. Registration results between D-CBCT and F-CBCT were compared. D-CBCT image geometry fidelity was tested. RESULTS: The mean peak signal to noise ratio of D-CBCT was 1.7 dB higher than SART-TV reconstructions (P < .001, SART-DDL vs SART-TV, 36.36 ± 0.55 dB vs 34.68 ± 0.28 dB). All D-CBCT images were recognized as clinically acceptable without significant difference with F-CBCT in subjective grading (P > .05). In clinical registration, the maximum translational and rotational difference was 1.8 mm and 1.7 degree respectively. The horizontal, vertical and sagittal geometry fidelity of D-CBCT were acceptable. CONCLUSIONS: The image quality, geometry fidelity and clinical application ability of D-CBCT are comparable to that of the F-CBCT for head-and-neck patients with 18% less projections by SART-DDL.