Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.

OBJECTIVE: This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. METHODS: A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. RESULTS: The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. CONCLUSION: The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.

Long-term Therapeutic Outcome and Prognostic Factors of Patients with Nasopharyngeal Carcinoma Receiving Intensity-modulated Radiotherapy: An Analysis of 608 Patients from Low-endemic Regions of China.

OBJECTIVE: To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT). METHODS: The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. RESULTS: The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively. CONCLUSION: IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

Hypo-fractionation radiotherapy normalizes tumor vasculature in non-small cell lung cancer xenografts through the p-STAT3/HIF-1 alpha signaling pathway.

BACKGROUND: Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT). METHODS: The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected. RESULTS: Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT. CONCLUSION: Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway.

Influence of CyberKnife Prescription Isodose Line on the Discrepancy of Dose Results Calculated by the Ray Tracing and Monte Carlo Algorithms for Head and Lung Plans: A Phantom Study.

Incorporation of the Monte Carlo (MC) algorithm in optimizing CyberKnife (CK) plans is cumbersome, and early models unconfgured MC calculations, therefore, this study investigated algorithm-based dose calculation discrepancies by selecting different prescription isodose lines (PIDLs) in head and lung CK plans. CK plans were based on anthropomorphic phantoms. Four shells were set at 2-60 mm from the target, and the constraint doses were adjusted according to the design strategy. After optimization, 30%-90% PIDL plans were generated by ray tracing (RT). In the evaluation module, CK plans were recalculated using the MC algorithm. Therefore, the dosimetric parameters of different PIDL plans based on the RT and MC algorithms were obtained and analyzed. The discrepancies (mean±SD) were 3.72%±0.31%, 3.40%±0.11%, 3.47%±0.32%, 0.17%±0.11%, 0.64%±3.60%, 7.73%±1.60%, 14.62%±3.21% and 10.10%±1.57% for D1%, D(mean), D98% and coverage of the PTV, DGI, V5, V3 and V1 in the head plans and -6.32%±1.15%, -13.46%±0.98%, -20.63%±2.25%, -34.78%±25.03%, 122.48%±175.60%, -12.92%±5.41%, 3.19%±4.67% and 7.13%±1.56% in the lung plans, respectively. The following parameters were signifcantly correlated with PIDL: dD98% at the 0.05 level and dDGI, dV5 and dV3 at the 0.01 level for the head plans; dD98% at the 0.05 level and dD1%, dD(mean), dCoverage, dDGI, dV5 and dV3 at the 0.01 level for the lung plans. RT may be used to calculate the dose in CK head plans, but when the dose of organs at risk is close to the limit, it is necessary to refer to the MC results or to further optimize the CK plan to reduce the dose. For lung plans, the MC algorithm is recommended. For early models without the MC algorithm, a lower PIDL plan is recommended; otherwise, a large PIDL plan risks serious underdosage in the target area.

Estimating intrafraction tumor motion during fiducial-based liver stereotactic radiotherapy via an iterative closest point (ICP) algorithm.

BACKGROUND: Tumor motion may compromise the accuracy of liver stereotactic radiotherapy. In order to carry out a precise planning, estimating liver tumor motion during radiotherapy has received a lot of attention. Previous approach may have difficult to deal with image data corrupted by noise. The iterative closest point (ICP) algorithm is widely used for estimating the rigid registration of three-dimensional point sets when these data were dense or corrupted. In the light of this, our study estimated the three-dimensional (3D) rigid motion of liver tumors during stereotactic liver radiotherapy using reconstructed 3D coordinates of fiducials based on the ICP algorithm. METHODS: Four hundred ninety-five pairs of orthogonal kilovoltage (KV) images from the CyberKnife stereo imaging system for 12 patients were used in this study. For each pair of images, the 3D coordinates of fiducial markers inside the liver were calculated via geometric derivations. The 3D coordinates were used to calculate the real-time translational and rotational motion of liver tumors around three axes via an ICP algorithm. The residual error was also investigated both with and without rotational correction. RESULTS: The translational shifts of liver tumors in left-right (LR), anterior-posterior (AP),and superior-inferior (SI) directions were 2.92 ± 1.98 mm, 5.54 ± 3.12 mm, and 16.22 ± 5.86 mm, respectively; the rotational angles in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were 3.95° ± 3.08°, 4.93° ± 2.90°, and 4.09° ± 1.99°, respectively. Rotational correction decreased 3D fiducial displacement from 1.19 ± 0.35 mm to 0.65 ± 0.24 mm (P<0.001). CONCLUSIONS: The maximum translational movement occurred in the SI direction. Rotational correction decreased fiducial displacements and increased tumor tracking accuracy.

Dosimetric Effect of Intrafraction Tumor Motion in Lung Stereotactic Body Radiotherapy Using CyberKnife Static Tracking System.

PURPOSE: We investigated the dosimetric effect of intrafraction tumor motion in lung stereotactic body radiotherapy using the CyberKnife static tracking system. METHODS: Four-dimensional computed tomography scans of a dynamic thorax phantom were acquired. Two motion ranges, 3 collimator sizes, and 4 treatment starting phases were investigated. Monte Carlo dose distributions were calculated on internal target volume with a treatment-specific setup margin for 6 Gy/1 fraction. Dosimetric effects of intrafractional tumor motion were assessed with Gafchromic films. γ (5%/3 mm), dose differences, and distance to agreement were analyzed. RESULTS: With 30 mm collimator plans, the measured dose passed the criteria γ (5%/3 mm) in all tumor motion ranges. The γ passing rates of the plans using 20 mm or 20+35 mm collimators were much lower than that with 30 mm collimator, especially with the 30 mm tumor motion range. The measured dose of 10 mm tumor motion ranges all passed the 90% criteria of γ (5%/3 mm), the results being much better than those of 30 mm tumor motion ranges, which were below 80%. The results of same delivered plan but treated with different starting phases varies greatly. CONCLUSION: Xsight Lung Tracking technique should be used with caution in lung cancer stereotactic body radiation therapy because the temporal dose variations can be significant.

Clinical characteristics of non-alcoholic fatty liver disease related hepatocellular carcinoma / 中国实用内科杂志

With the rising incidence, nonalcoholic fatty liver disease associated hepatocellular carcinoma(NAFLD-HCC) has become the main type of liver cancer. Therefore, to improve the level of clinical diagnosis and treatment of NAFLD-HCC is of great value. This paper summarized the clinical characteristics of NAFLD-HCC, and has found that the NAFLD-HCC has a special nature course,without typical clinical manifestation; it is common in male, often accompanied with the metabolic syndrome, with single tumor and good differentiation. Serology, CT imaging and pathology are important in diagnosis of NAFLD-HCC. Improve living habits and strengthen exercise can prevent the occurrence of NAFLD-HCC. Drug and surgical treatment is still the most important means to treat NAFLD-HCC, while the effects of those treatments used in NAFLD-HCC have no significant difference compared with that used in other types of liver cancer. To summarize clinical features will help improve the level of diagnosis and treatment of NAFLD-HCC.It's necessary to constantly explore the pathogenesis of NAFLD-HCC in order to formulate the individualized prevention strategy of NAFLD-HCC which is of great significance.

Double-arc volumetric modulated therapy improves dose distribution compared to static gantry IMRT and 3D conformal radiotherapy for adjuvant therapy of gastric cancer.

BACKGROUND: The objective of this study was to compare the dose distributions of RapidArc (RA), static gantry intensity-modulated radiotherapy (IMRT), and three-dimensional conformal radiotherapy (3DCRT) as adjuvant radiotherapy modalities for the treatment of gastric cancer. METHODS: Fifteen patients with gastric cancer that underwent limited lymphadenectomy of perigastric lymph nodes were included in this study. Dosimetric values for a total dose of 45 Gy (1.8 Gy/day) were calculated for the RapidArc, IMRT, and 3DCRT modalities. The following parameters were compared: D99%, D1%, V95%, V107%, and conformity and homogeneity index values (CI and HI, respectively) for the planned target volume (PTV). Dose volume histogram (DVH) and dose distribution of the organs at risk (OAR), as the maximal dose to the spinal cord, V30 and V40 of the small bowel, and V20, V30 of liver and kidney were also assessed respectively. RESULTS: RA, IMRT, and 3DCRT all achieved desirable PTV coverage. However, RA and IMRT significantly decreased D1% and V107%, and provided better CI and HI values compared with 3DCRT (P <0.05). Moreover, RA also achieved a significantly lower maximum dose for the spinal cord, liver V30, and kidney V20 compared to IMRT and 3DCRT; while the mean dose for these three organ types did not differ for the RA, IMRT, and 3DCRT plans. CONCLUSIONS: Both RA and IMRT achieved favorable PTV coverage compared to 3DCRT. In addition, RA achieved better dosimetry than IMRT and 3DCRT, and provided better protection for the spinal cord, liver, and kidneys.