Sen Bai

The clinical feasibility and effect of online cone beam computer tomography-guided intensity-modulated radiotherapy for nasopharyngeal cancer.

BACKGROUND AND PURPOSE Online adaptive correction in image-guided intensity-modulated radiotherapy appeared to be a promising approach for precision radiation treatment in head and neck tumors. This protocol was designed to evaluate the clinical feasibility and effect of online cone beam computed tomography (CBCT) guidance in IMRT of nasopharyngeal cancer (NPC). METHODS AND MATERIALS The Elekta Synergy system, which integrates an X-ray volumetric imager (XVI), was used to deliver radiation treatment for 22 cases of NPC. The acquired CBCT was registered to the planning CT for online and offline analysis. The systematic and random setup errors, as well as planning target volume (PTV) margin, were calculated at different correction threshold levels. The impact of online setup correction on dosimetry was evaluated by simulation of pre-correction errors. RESULTS The correction-of-setup-errors frequencies for 1, 2 and 3mm thresholds were 41.3-53.9%, 12.7-21.2% and 6.3-10.3%, respectively. Online correction was effective at the 2mm threshold level for all three axes. The pre-correction systematic errors for the whole group ranged 1.1-1.3mm, and the random errors were also 1.1-1.3mm. After online correction, the systematic and random errors ranged 0.4-0.5mm and 0.7-0.8mm, respectively, in the three directions. The PTV margins for the pre-correction, pretreatment and post-treatment positions were 3.5-4.2mm, 1.6-1.8mm and 2.5-3.2mm, respectively, in three directions. Analysis of hypothetical dosimetric change due to a translational isocenter shift of 3mm showed that if no correction was applied, the mean maximum dose to both the brain stem and spinal cord would be increased by 10Gy, the mean dose to the left and right parotids would be increased by 7.8 and 8.5Gy, respectively, and the dose to target volumes would be decreased: 4Gy for 95% GTV and 5.6Gy for 95% CTV(60.) CONCLUSIONS CBCT-based online correction increased the accuracy of IMRT for NPC and reduced irradiated margins, by decreasing both the systematic and random errors. Online CBCT correction reduces the radiation dose to normal tissue and creates room for further dose escalation of tumors.

Detection of intrafractional tumour position error in radiotherapy utilizing cone beam computed tomography

PURPOSE To study the intrafraction tumour position error utilizing cone beam CT (CBCT) in patients receiving radiotherapy. METHODS AND MATERIALS Fifty-four patients were treated with Elekta Synergy S system, including 19 head and neck, 25 thoracic and 10 abdominal-pelvic tumours. All patients received CBCT after initial setup and some of them received CBCT after correction and after treatment. CBCT were registered to planning CT and errors of isocenter position on the left-to-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were analyzed. RESULTS After treatment the systematic (Sigma) and random uncertainty (sigma) increased, the increments of tumour Sigma were 0.1-0.3, 0.2-0.5 and 0.2-0.6 mm, respectively, while the increments of sigma were 0.1-0.3, 0.2-0.4 and 0.1-0.4 mm, respectively, for the head and neck, thoracic and abdominal-pelvic tumours. Based on 380 paired pre- and post-treatment CBCT, the intrafraction errors (mean+/-SD) in the LR, SI and AP directions were -0.1+/-0.9, -0.3+/-1.0 and -0.2+/-0.7 mm, respectively, for head and neck tumours, -0.1+/-1.2, -0.1+/-1.9 and 0.1+/-1.3 mm, respectively, for thoracic tumours, -0.1+/-1.1, 0.2+/-1.4 and -0.1+/-1.5 mm, respectively, for abdominal-pelvic tumours. Isotropic planning margins of 3.4, 6.1 and 5.4 mm were generated with linear addition of internal margin (IM) to CTV for the head and neck, thoracic and abdominal-pelvic tumours, respectively, while margins were only 2.4, 4.4 and 3.9 mm, respectively, if IM was added in quadrature. CONCLUSIONS Utilizing CBCT measurements before and after treatment to detect intrafraction tumour position errors was clinically feasible. The detected intrafraction errors could be applied to improve the accuracy of radiation delivery.

Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis

BackgroundTreatments for cancer spinal metastasis were always palliative. This study was conducted to investigate the safety and effectiveness of IG-IMRT for these patients.Methods10 metastatic lesions were treated with conventionally-fractionated IG-IMRT. Daily kilovoltage cone-beam computed tomography (kV-CBCT) scan was applied to ensure accurate positioning. Plans were evaluated by the dose-volume histogram (DVH) analysis.ResultsBefore set-up correction, the positioning errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes were 0.3 ± 3.2, 0.4 ± 4.5 and -0.2 ± 3.9 mm, respectively. After repositioning, those errors were 0.1 ± 0.7, 0 ± 0.8 and 0 ± 0.7 mm, respectively. The systematic/random uncertainties ranged 1.4–2.3/3.0–4.1 before and 0.1–0.2/0.7–0.8 mm after online set-up correction. In the original IMRT plans, the average dose of the planning target volume (PTV) was 61.9 Gy, with the spinal cord dose less than 49 Gy. Compared to the simulated PTVs based on the pre-correction CBCT, the average volume reduction of PTVs was 42.3% after online correction. Also, organ at risk (OAR) all benefited from CBCT-based set-up correction and had significant dose reduction with IGRT technique. Clinically, most patients had prompt pain relief within one month of treatment. There was no radiation-induced toxicity detected clinically during a median follow-up of 15.6 months.ConclusionIG-IMRT provides a new approach to treat cancer spinal metastasis. The precise positioning ensures the implementation of optimal IMRT plan, satisfying both the dose escalation of tumor targets and the radiation tolerance of spinal cord. It might benefit the cancer patient with spinal metastasis.

Lung tumor reproducibility with active breath control (ABC) in image-guided radiotherapy based on cone-beam computed tomography with two registration methods

PURPOSE To study the inter- and intrafraction tumor reproducibility with active breath control (ABC) utilizing cone-beam computed tomography (CBCT), and compare validity of registration with two different regions of interest (ROI). METHODS AND MATERIALS Thirty-one lung tumors in 19 patients received conventional or stereotactic body radiotherapy with ABC. During each treatment, patients had three CBCT scanned before and after online position correction and after treatment. These CBCT images were aligned to the planning CT using the gray scale registration of tumor and bony registration of the thorax, and tumor position uncertainties were then determined. RESULTS The interfraction systematic and random translation errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were 3.6, 4.8, and 2.9mm; 2.5, 4.5, and 3.5mm, respectively, with gray scale alignment; 1.9, 4.3, 2.0mm and 2.5, 4.4, 2.9mm, respectively, with bony alignment. The interfraction systematic and random rotation errors with gray scale and bony alignment groups ranged from 1.4° to 3.0° and 0.8° to 2.3°, respectively. The intrafraction systematic and random errors with gray scale registration in LR, SI, AP directions were 0.9, 2.0, 1.8mm and 1.5, 1.7, 2.9mm, respectively, for translation; 1.5°, 0.9°, 1.0° and 1.2°, 2.2°, 1.8°, respectively, for rotation. The translational errors in SI direction with bony alignment were significantly larger than that of gray scale (p<0.05). CONCLUSIONS With CBCT guided online correction the interfraction positioning errors can be markedly reduced. The intrafraction errors were not diminished by the use of ABC. Rotation errors were not very remarkable both inter- and intrafraction. Gray scale alignment of tumor may provide a better registration in SI direction.

In vivo99mTc-HYNIC-annexin V imaging of early tumor apoptosis in mice after single dose irradiation

BackgroundApoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. 99mTc-HYNIC-annexinV has been reported as a promising agent for in vivo apoptosis imaging. The purpose of this study is to evaluate the feasibility of in vivo99mTc-HYNIC-annexinV imaging of radiation- induced apoptosis, and to investigate its correlation with radiosensitivity.MethodsTen days after inoculation of tumor cells in the right upper limbs, the mice were randomly divided into two groups. The imaging group (4 mice each level, 4 dose levels) was injected with 4-8 MBq 99mTc-HYNIC-annexinV 24 hours after irradiation and imaged 1 hr post-injection, and the mice were sacrificed immediately after imaging for biodistribution analysis of annexin V. The observation group (4 mice each level, 2 dose levels) was only observed for tumor regression post-radiation. The number of apoptotic cells in a tumor was estimated with TUNEL assay.ResultsThe 99mTc-HYNIC-annexin V uptake in E14 lymphoma significantly increased as the radiation dose escalated from 0 to 8 Gy, and significantly correlated with the number of TUNEL-positive cells (r = 0.892, P < 0.001). The Annexin-V uptake and the number of TUNEL-positive cells in El4 lymphoma were significantly greater than those in S180 sarcoma. With 8 Gy, S180 sarcoma tumor showed scanty apoptosis and less shrinkage while El4 lymphoma showed remarkable apoptosis and complete remission.Conclusion99mTc-HYNIC-annexinV in vivo imaging is a feasible method to detect early radiation-induced apoptosis in different tumors, and might be predictive for radiation sensitivity.

Hypofraction radiotherapy of liver tumor using cone beam computed tomography guidance combined with active breath control by long breath-holding

BACKGROUND AND PURPOSE To evaluate the feasibility and validity of cone beam computed tomography (CBCT) and active breath control (ABC) by long breath-holding in hypofraction radiotherapy of liver tumor. METHODS AND MATERIALS Twenty-four patients received hypofraction radiotherapy of liver tumor with long breath-holding at end-inhale; four prescriptions were used: 6 Gy×7 (n=8), 10 Gy×4 (n=7), 5 Gy×9 (n=6), 4 Gy×10 (n=3). For each fraction, all patients received pre-correction CBCT scans with ABC, some patients received post-correction and post-treatment CBCT. The interfraction and intrafraction liver positioning errors on medial-lateral (ML), cranial-caudal (CC) and anterior-posterior (AP) directions were obtained. The theoretic margin from clinical target volume (CTV) to planning target volume (PTV) was calculated based on post-treatment error. The dosimetric parameters of PTV and normal tissue were compared between ABC and free breathing (FB). RESULTS The interfraction error in liver positioning showed system errors (Σ) of 3.18 mm (ML), 6.80 mm (CC) and 3.05 mm (AP); random error (σ) of 3.03 mm (ML), 6.78 mm (CC) and 3.62 mm (AP). These errors were significantly reduced with CBCT guided online correction. The intrafraction systematic error was 0.72 mm (ML), 2.21 mm (CC), 1.49 mm (AP), and random error was 2.30 mm (ML), 3.58 mm (CC), 2.49 mm (AP). Dosimetric parameters such as PTV, the livers volume included by 23, 30 Gy isodose curve (V23, V30), mean dose to normal liver (MDTNL) and mean dose to cord were significantly larger for FB (P<0.05). CONCLUSION Liver radiotherapy with long time breath-holding at end-inhale is an effective method to reduce liver motion, PTV and dose to normal tissue. Interfraction and intrafraction liver positioning errors were substantial. CBCT guided online correction of positioning error is recommended for liver radiotherapy with end-inhale ABC.

Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathing control

BackgroundTo study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung.Methods32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed.ResultsThe pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis.ConclusionThe positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.

Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patients case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V20/30, and mean dose of the left kidney, as well as the V20/30 of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V20 of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.

Evaluation of positioning accuracy of four different immobilizations using cone-beam CT in radiotherapy of non-small-cell lung cancer.

PURPOSE To evaluate the positioning accuracy of four different immobilizations by use of cone-beam computed tomography guidance for radiotherapy of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Sixty-seven patients with NSCLC received conventional or stereotactic body radiotherapy. Of these, 30 were immobilized with a thermoplastic frame (TF), 16 with a thermoplastic frame and active breathing control (TF-ABC), 7 with a stereotactic body frame (SBF), and 14 with a stereotactic body frame and active breathing control (SBF-ABC). Cone-beam computed tomography scans at initial setup and after correction were registered to planning computed tomography. The positional errors in the left-to-right, superior-inferior, and anterior-posterior directions were analyzed. The planning target volume margins were calculated. RESULTS The precorrection systematic and random errors ranged from 1.9 to 4.2 mm for TF, 1.9 to 4.3 mm for SBF, 1.2 to 5.8 mm for TF-ABC, and 2.3 to 3.9 mm for SBF-ABC. The postcorrection systematic and random errors ranged from 0.3 to 1.9 mm for the four immobilizations. The planning target volume margins (conventional vs. stereotactic body radiotherapy) were 15.6 vs. 13.9 mm (TF), 14.9 vs. 14.8 mm (TF-ABC), 14.4 vs. 13.4 mm (SBF), and 9.9 vs. 9.4 mm (SBF-ABC) before correction and 7.3 vs. 6.9 mm (TF), 4.0 vs. 3.8 mm (TF-ABC), 7.5 vs. 7.1 mm (SBF), and 4.5 vs. 4.2 mm (SBF-ABC) after correction. CONCLUSIONS The positioning accuracies of SBF and TF were similar. Active breathing control increased positioning error but reduced internal margin. Cone-beam computed tomography online correction improved the positioning accuracy of NSCLC patients.

Effect of MLC leaf position, collimator rotation angle, and gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma

The purpose of this study was to investigate the effect of multileaf collimator (MLC) leaf position, collimator rotation angle, and accelerator gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma. To compare dosimetric differences between the simulating plans and the clinical plans with evaluation parameters, 6 patients with nasopharyngeal carcinoma were selected for simulation of systematic and random MLC leaf position errors, collimator rotation angle errors, and accelerator gantry rotation angle errors. There was a high sensitivity to dose distribution for systematic MLC leaf position errors in response to field size. When the systematic MLC position errors were 0.5, 1, and 2mm, respectively, the maximum values of the mean dose deviation, observed in parotid glands, were 4.63%, 8.69%, and 18.32%, respectively. The dosimetric effect was comparatively small for systematic MLC shift errors. For random MLC errors up to 2mm and collimator and gantry rotation angle errors up to 0.5°, the dosimetric effect was negligible. We suggest that quality control be regularly conducted for MLC leaves, so as to ensure that systematic MLC leaf position errors are within 0.5mm. Because the dosimetric effect of 0.5° collimator and gantry rotation angle errors is negligible, it can be concluded that setting a proper threshold for allowed errors of collimator and gantry rotation angle may increase treatment efficacy and reduce treatment time.