Functional lung imaging in thoracic tumor radiotherapy: Application and progress.

Radiotherapy plays an irreplaceable and unique role in treating thoracic tumors, but the occurrence of radiation-induced lung injury has limited the increase in tumor target doses and has influenced patients' quality of life. However, the introduction of functional lung imaging has been incorporating functional lungs into radiotherapy planning. The design of the functional lung protection plan, while meeting the target dose requirements and dose limitations of the organs at risk (OARs), minimizes the radiation dose to the functional lung, thus reducing the occurrence of radiation-induced lung injury. In this manuscript, we mainly reviewed the lung ventilation or/and perfusion functional imaging modalities, application, and progress, as well as the results based on the functional lung protection planning in thoracic tumors. In addition, we also discussed the problems that should be explored and further studied in the practical application based on functional lung radiotherapy planning.

Different functional lung-sparing strategies and radiotherapy techniques for patients with esophageal cancer.

Background: Integration of 4D-CT ventilation function images into esophageal cancer radiation treatment planning aimed to assess dosimetric differences between different functional lung (FL) protection strategies and radiotherapy techniques. Methods: A total of 15 patients with esophageal cancer who had 4D-CT scans were included. Lung ventilation function images based on Jacobian values were obtained by deformation image registration and ventilation imaging algorithm. Several different plans were designed for each patient: clinical treatment planning (non-sparing planning), the same beam distribution to FL-sparing planning, three fixed-beams FL-sparing intensity-modulated radiation therapy (IMRT) planning (5F-IMRT, 7F-IMRT, 9F-IMRT), and two FL-sparing volumetric modulated arc therapy (VMAT) planning [1F-VMAT (1-Arc), 2F-VMAT (2-Arc)]. The dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) were compared and focused on dosimetric differences in FL. Results: The FL-sparing planning compared with the non-sparing planning significantly decreased the FL-Dmean, V5-30 and Lungs-Dmean, V10-30 (Vx: volume of receiving ≥X Gy), although it slightly compromised PTV conformability and increased Heart-V40 (P< 0.05). The 5F-IMRT had the lowest PTV-conformability index (CI) but had a lower Lungs and Heart irradiation dose compared with those of the 7F-IMRT and 9F-IMRT (P< 0.05). The 2F-VMAT had higher PTV-homogeneity index (HI) and reduced irradiation dose to FL, Lungs, and Heart compared to those of the 1F-VMAT planning (P< 0.05). The 2F-VMAT had higher PTV conformability and homogeneity and decreased FL-Dmean, V5-20 and Lungs-Dmean, V5-10 but correspondingly increased spinal cord-Dmean compared with those of the 5F-IMRT planning (P< 0.05). Conclusion: In this study, 4D-CT ventilation function image-based FL-sparing planning for esophageal cancer can effectively reduce the dose of the FL. The 2F-VMAT planning is better than the 5F-IMRT planning in reducing the dose of FL.

Functional Liver Imaging in Radiotherapy for Liver Cancer: A Systematic Review and Meta-Analysis.

Backgrounds: Functional liver imaging can identify functional liver distribution heterogeneity and integrate it into radiotherapy planning. The feasibility and clinical benefit of functional liver-sparing radiotherapy planning are currently unknown. Methods: A comprehensive search of several primary databases was performed to identify studies that met the inclusion criteria. The primary objective of this study was to evaluate the dosimetric and clinical benefits of functional liver-sparing planning radiotherapy. Secondary objectives were to assess the ability of functional imaging to predict the risk of radiation-induced liver toxicity (RILT), and the dose-response relationship after radiotherapy. Results: A total of 20 publications were enrolled in descriptive tables and meta-analysis. The meta-analysis found that mean functional liver dose (f-MLD) was reduced by 1.0 Gy [95%CI: (-0.13, 2.13)], standard mean differences (SMD) of functional liver volume receiving ≥20 Gy (fV20) decreased by 0.25 [95%CI: (-0.14, 0.65)] when planning was optimized to sparing functional liver (P >0.05). Seven clinical prospective studies reported functional liver-sparing planning-guided radiotherapy leads to a low incidence of RILD, and the single rate meta-analysis showed that the RILD (defined as CTP score increase ≥2) incidence was 0.04 [95%CI: (0.00, 0.11), P <0.05]. Four studies showed that functional liver imaging had a higher value to predict RILT than conventional anatomical CT. Four studies established dose-response relationships in functional liver imaging after radiotherapy. Conclusion: Although functional imaging modalities and definitions are heterogeneous between studies, but incorporation into radiotherapy procedures for liver cancer patients may provide clinical benefits. Further validation in randomized clinical trials will be required in the future.

4D-CT reconstruction based on pulmonary average CT values.

To date, commercial 4D-CT systems typically depend on an external respiratory monitoring device. Immobilizing patients in a thermoplastic mask while receiving radiotherapy may result in a failure of 4D-CT reconstruction. The aim of this study is to investigate the feasibility of 4D-CT reconstruction based on a method using pulmonary average CT values (ACV) without an external respiratory monitoring device. The ACV of the whole lung assumes cyclical variation during respiration. Phases of CT images were identified by calculating the ACV over time. Subsequently, five sets of 4D-CT images based on a Real-time Position Management (RPM) system were selected to verify the ACV method. The entire lung CT datasets of another sixteen free-breathing patients were acquired in Cine scan mode for multiple couch positions. The phase of every CT image was identified and re-sorted into different phase 4D-CT volumes by analyzing the time dependence of the corresponding ACVs. This paper demonstrates the ACV method using the 4D-CT data sets based on the RPM system. Convenient and reliable 4D-CT reconstruction can be accomplished without any external respiratory monitoring device using ACVs.

The feasibility of mapping dose distribution of 4DCT images with deformable image registration in lung.

Calculating an accurate cumulative dose through individual phases for four-dimensional computed tomography (4DCT) images from the lung is time-consuming. Although the dose distribution of different phases is similar, copying the dose distribution of one phase directly to another phase would yield a dosimetric error of approximately 4% without further optimization. To reduce the dosimetric error, three-dimensional B-spline elastic deformable image registration (DIR) was used to quickly obtain a relatively accurate cumulative dose of 4DCT images acquired from ten lung cancer patients. The dose distribution of the end-expiration phase was mapped to the end-inspiration phase using DIR. The mapped dose in the end-inspiration phase was then compared with the directly copied dose by analysis (3cm/3%) and the t-test. The results showed that optimization using DIR was significantly better in the average pass rate (by 0.6-4.7%). Our results indicate it is feasible to map the dose distribution of 4DCT images in lung with DIR, and that the motion amplitude of individual respiratory and different DIR algorithms affect the differences between the mapped and actual dose.

Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord.

[Validation of an improved Demons deformable registration algorithm and its application in re-contouring in 4D-CT].

OBJECTIVE: To validate the efficiency and accuracy of an improved Demons deformable registration algorithm and evaluate its application in contour recontouring in 4D-CT. METHODS: To increase the additional Demons force and reallocate the bilateral forces to accelerate convergent speed, we propose a novel energy function as the similarity measure, and utilize a BFGS method for optimization to avoid specifying the numbers of iteration. Mathematical transformed deformable CT images and home-made deformable phantom were used to validate the accuracy of the improved algorithm, and its effectiveness for contour recontouring was tested. RESULTS: The improved algorithm showed a relatively high registration accuracy and speed when compared with the classic Demons algorithm and optical flow based method. Visual inspection of the positions and shapes of the deformed contours agreed well with the physician-drawn contours. CONCLUSION: Deformable registration is a key technique in 4D-CT, and this improved Demons algorithm for contour recontouring can significantly reduce the workload of the physicians. The registration accuracy of this method proves to be sufficient for clinical needs.

[In vitro induced and expanded Epstein Barr virus-specific cytotoxic T lymphocytes can specifically kill nasopharyngeal carcinoma cells].

OBJECTIVE: To establish a method for efficient induction and expansion of Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) in vitro and evaluate the possibility of using this strategy for treatment of nasopharyngeal carcinoma (NPC). METHODS: EBV-transformed B lymphoblastoid cells (BLCLs) were used as the antigen stimuli and antigen-presenting cells. EBV-specific CTL was induced by co-culture of the autologous peripheral blood mononuclear cells (PBMCs) and the irradiated BLCLs, and expanded with a cocktail method consisting of OKT-3, irradiated homologous PBMC, and IL-2. The specific activity of the CTL against the NPC cells was measured with MTT assay. RESULTS: EBV-specific CTL was successfully induced and expanded by 600 folds. The killing efficiency of the CTL was 76% for autologous BLCLs, 13% for homologous BLCLs, 51% for autologous NPC cells, and 27% for homologous CNE cell line, and after expansion, the corresponding killing efficiencies were 63%, 25%, 49%, and 33%, respectively. The non-specific killing only slightly increased after the expansion. CONCLUSION: EBV-specific CTL can be successfully induced and expanded in vitro for specific killing of autologous NPC cells, suggesting the potential of this strategy in the treatment of NPC.

[Design of a 3D afterloading brachytherapy simulation system based on CT images].

OBJECTIVE: To design a new afterloading brachytherapy simulation system based on CT images. METHODS: This paper mainly focuses on the anthropomorphic pelvic phantom spiled by three pipelines and the nasopharyngeal carcinoma spiled by two pipelines. Microsoft Visual C++ was used to parse CT images for some information, then to reconstruct pipelines in the body of phantom or the patient and to give the three-dimensional coordinate of dwelling points. The dose distribution displayed on CT images was processed by the dose distribution calculation methods near single afterloading source and the dose optimization methods. VTK technology was used in the 3D display in the system. RESULTS: According to the reference points applied by doctors, the system can calculate reversely the dwelling time of dwelling points in pipelines and get satisfying dose distribution on CT images. Besides, it can reflect the 3D relationship between the dose volume and the normal tissues. CONCLUSIONS: This system overcomes some deficiencies of 2D afterloading brachytherapy simulation system based on X-ray films which are used widely in China. It supplies 3D display of dose distribution for clinical doctors. At present, the system is being tested in clinics.

[Comparison of the irradiation doses for IMRT and conventional radiotherapy in nasopharyngeal carcinoma patients].

OBJECTIVE: To compare the dose difference in irradiation dose between nasopharyngeal cancer patients receiving conventional radiotherapy (CR) and intensity-modulated radiotherapy (IMRT). METHODS: The various IMRT and the CR plans for patients with nasopharyngeal carcinoma were created by a three-dimensional treatment planning system (3D-TPS). The dose-volume histograms (DVH) of normal tissues and the total number of irradiation monitor units (MU) were calculated by 3D-TPS. The treatment was delivered with 6 MV photons using a "step-and-shoot" technique on a linear accelerator. The X-ray leakage and scattered dose (LSD) at the dmax (maximal dose depth) in water were measured by dosimeter and ion chamber. The dose delivered to normal tissue adjacent to the treatment site at a certain distance was estimated by using LSD and the total MU for different radiotherapy methods. RESULTS: To IMRT patients, the volumes of normal tissues receiving the dose less than 28 Gy and higher than 35 Gy were 1.43-1.81 and 0.70-0.30 times those of CR patients respectively. The LSD irradiated that to the IMRT patients was about two times of the CR patients. CONCLUSION: The dose received by normal tissues in IMRT is two times that in CR.