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Objective To perform a systematic review and Meta-analysis on volumetric and dosimetric changes in target volumes and organs at risk (OARs) in adaptive radiotherapy (ART) for patientswith head and neck cancer (HNC), and to investigate the role of ART in the treatment of HNC. Methods Literature retrieval was performed to include related studies, and the parameters of primary tumor, GTV-T and GTV-N, parotid volume, D95 and Dmean of target volumes, Dmean of ipsilateral and contralateral parotid volume (I-PG and C-PG), and Dmax of the spinal cord and brainstem. Results A total of 17 studies involving 336 patients were included in the meta-analysis. Primary tumor and parotid volume changed significantly. The volumes of GTV-T, GTV-N, and I-PG were significantly reduced during the 15-20th radiotherapy and after the 20th radiotherapy (P<0.05), and the C-PG was significantly reduced after the 20th radiotherapy (P=0.004). The analysis of actual dose showed that the D95 and Dmean of primary tumor showed no significant differences, and during the 15-20th radiotherapy, the Dmax of the spinal cord was increased by 2.26 Gy (P=0.000), while the Dmax of the brainstem showed no significant changes before the 20th radiotherapy and was increased by 1.78 Gy after the 25th radiotherapy (P=0.020). In addition, the Dmean of I-PG was increased by 2 Gy during the 20-25th radiotherapy (P=0.0001), and the Dmean of C-PG was increased before the 20th radiotherapy and showed no significant changes after the 25th radiotherapy (P=0.110). The dosimetric analysis of ART showed that the Dmax of the spinal cord and brainstem was reduced significantly (spinal cord:MD=-2.15, 95% CI-3.12 to -1.18,P=0.000;brainstem:MD=-2.20, 95% CI-3.32 to -1.09, P=0.000). The Dmean of I-PG was reduced by about 3.5 Gy, and the sensitivity analysis revealed that the results of Dmean of C-PG were unstable. Conclusions The volumes of primary tumors and parotid glands change significantly, and the actual doses of OARs (Dmax of the spinal cord and brainstem and Dmean of the parotid glands) significantly increase, while the doses of GTV-T and GTV-N show no significant changes. ART can effectively protect the OARs, and patients with locally advanced HNC who receive concurrent chemoradiotherapy can obtain good dose gains from ART plan performed during the 15-20th radiotherapy and at about the 25th radiotherapy.
Objective To investigate the safety and preliminary effect of postoperative intensity-modulated radiotherapy (IMRT) combined with concurrent weekly paclitaxel-nedaplatin chemotherapy for patients with esophageal squamous cell carcinoma. Methods A total of 52 patients who were treated from 2010 to 2013 were enrolled. The clinical target volume of IMRT included tumor beds and corresponding lymphatic drainage regions at high risk, and the total radiotherapy dose was 50-60 Gy, 2.0 Gy/fraction, 5 fractions per week. The concurrent chemotherapy consisted of nedaplatin 25 mg/m2 on D1 and paclitaxel 45-50 mg/m2 on D1 and was repeated every week during radiotherapy. Common Terminology Criteria for Adverse Events 4.0 was used to evaluate adverse events, and the Kaplan-Meier method was used for survival analysis. Results All the patients had good tolerance to the treatment, and 51 patients (98%) completed radiotherapy according to the scheduled regimen. The median number of chemotherapy cycles was 4, and 42 patients (81%) completed ≥3 cycles of chemotherapy. Most adverse events were of grade 1-2, and grade 3 adverse events were leucopenia (29%), radiation esophagitis (10%), and anastomotic stenosis (4%). One patient (2%) experienced grade 5 gastroesophageal bleeding. Of all the patients, the median survival time was 38.7 months, and the 1-, 2-, 3-, and 4-year overall survival rates were 83%, 64%, 51%, and 38%, respectively. The overall recurrence rate was 46.2%, and the locoregional recurrence rate and distant metastasis rate were 15% and 37%, respectively. Conclusions Postoperative IMRT combined with concurrent weekly paclitaxel-nedaplatin chemotherapy for patients with esophageal squamous cell carcinoma is safe and effective, and large-scale prospective randomized studies are needed.
Objective To investigate the influence of three-dimensional radiotherapy dose determined by organ-lesion combination for the primary tumor of oligometastatic stage Ⅳ non-small cell lung cancer (NSCLC) and related factors on survival. Methods Oligometastasis was defined as the metastatic lesion in only one organ or 1 metastatic lesion in each of two organs. A total of 115 patients were enrolled,and the association of dose and related factors with overall survival was investigated. The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis,and the Cox regression model was used for multivariate analysis. Results Of all patients,the median survival time (MST) was 14 months,and the 1-,2-,and 3-year overall survival (OS) rates were 55.7%,18.3%,and 11.5%,respectively. All the patients,the patients benefiting from two-cycle chemotherapy,and the patients benefiting from chemoradiotherapy showed prolonged MST,and in patients receiving a primary tumor dose of ≥63 Gy or<63 Gy,the MST was 17 months and 13 months (P=0.046),17 months and 13 months (P=0.037),and 18 months and 14 months (P=0.022),respectively. Radiotherapy for metastatic lesion and effective treatment for primary tumor tended to prolong survival time,and the MST was 17 months and 13 months,respectively (P=0.055 and 0.065).The patients receiving 4-6 cycles of chemotherapy had an MST of 16 months and 13 months,respectively (P=0.165).The patients who received effective chemoradiotherapy,had a primary tumor volume of<120.1 cm3,and had improvement in Karnofsky Performance Scale (KPS) after treatment showed a prolonged MST compared with those who did not respond to chemoradiotherapy and had a large primary tumor volume and a reduction in KPS (15 months vs. 12 months,P=0.036;17 months vs. 11 months,P=0.002;14 months vs. 10 months,P=0.031).The multivariate analysis showed that primary tumor dose and volume (P=0.020 and 0.001) and the change in KPS after treatment (P=0.021) significantly affected survival. Conclusions The doses of chemotherapy and concurrent radical radiotherapy determined by organ-lesion combination for oligometastatic stage Ⅳ NSCLC can significantly prolong survival time,and primary tumor volume and KPS after treatment are the independent prognostic factors for survival.
Objective To identify the incidence and risk factors for upper extremity lymphedema within 2 years after surgery in patients with breast cancer. Methods A follow-up study was performed among 157 patients who newly received surgical treatment for breast cancer. Norman questionnaire and circumference measurement were used to evaluate the volume of the upper limb before treatment and at 1, 3, 6, 12, 18, and 24 months after treatment. The incidence of lymphedema was calculated. Based on the results of circumference measurement, the log-rank test and Cox regression were used to analyze the risk factors for lymphedema. Results A total of 141 patients were finally enrolled as subjects. The incidence rates of lymphedema at 1, 3, 6, 12, 18, and 24 months after surgery were 3.5%, 9.2%, 13.5%, 24.8%, 28.4%, and 30.5% by Norman questionnaire, and 1.4%, 3.5%, 9.2%, 20.6%, 27.0%, and 27.7% by circumference measurement. At 24 months after surgery, 31(22.0%) out of 39 patients with lymphedema had mild lymphedema. Axillary lymph node dissection (ALND), radiotherapy, modified radical mastectomy (MRM), and the number of removed axillary lymph nodes were independent risk factors for lymphedema (HR=13.58, 95% CI:2.17-85.00;HR=3.54, 95% CI:1.13-11.07;HR=2.19, 95% CI:1.07-4.49;HR=1.11, 95% CI:1.05-1.16). Conclusions The incidence of lymphedema associated with breast cancer increases gradually within 2 years after surgery, especially fast in the first year. ALND, radiotherapy, MRM, and the number of removed axillary lymph nodes are independent risk factors for lymphedema.
Objective To investigate a simple and easy method to maintain a stable urine volume and consistent bladder filling during immobilization, CT scanning, plan designing, and radiotherapy using an ultrasonic bladder capacity scanner (BS). Methods A total of 66 patients with pelvic tumor who were admitted to our hospital and received radiotherapy from 2013 to 2014 were enrolled and required to drink 500 ml water after emptying the bladder. BS was used to measure bladder capacity at four time points. Before radiotherapy, 62 patients with pelvic tumor were randomly divided into two groups in a single-blind trial. Both groups were asked to empty the bladder, drink 500 ml water, and wait for a subjective feeling of urgency of urination. The 42 patients in group 1 were asked to hold urine, and bladder capacity was measured and urine volume was recorded when patients complained of “urgency of urination”. The patients in group 2 were told that urine volume should reach the standard in plan designing, and BS was used to determine whether the standard was reached. Results The time from bladder emptying to the subjective feeling of urgency of urination ranged from 0.5 to 1.5 hours;when the patients had a subjective feeling of urgency of urination, the urine volume ranged from 30 to 500 ml. In group 1, when the patients had a subjective feeling of urgency of urination, the difference between the bladder capacity measured and that in plan designing was 30.6%, while in group 2, the difference was 12.6%. Conclusions The use of BS in monitoring bladder capacity helps patients to develop a stable feeling of urgency of urination and reach the bladder capacity in plan designing and thus maintain a consistent degree of bladder filling.
Objective As a classical approach for hyperthermic ablation,microwave ablation (MWA) has been widely used in the treatment of tumors that cannot be removed by traditional surgery. MWA devitalizes the neighboring tissue and kills tumor cells by thermal diffusion. In the last two decades,this technique has been improved for treating malignant bone tumor in our institute. In situ ablation has already replaced en bloc resection and achieved satisfactory treatment outcomes. This study explores whether tumor cell death induced by MWA would cause the release of immunogenic tumor antigens and tumor-specific immune responses. Methods Three models of MWA were established using osteosarcoma cell lines from the mouse,rat,and human,respectively. The expression of immunogenic molecules was measured during in vitro and in situ ablation with different ablation time and group design. Results The injection of tumor vaccines made from tumor cells or supernatant treated with in vitro ablation resulted in substantial inhibition of tumor cell growth in tumor-bearing animal models. The CD8+ T cells induced by vaccines played a key role in the process. The effector cells released cytokines,IFN-γ and TNF-α,to inhibit tumor cell growth and also trigger Fas/FasL-mediated apoptosis. Conclusions MWA-treated osteosarcoma cells can be used to induce specific antitumor immunogenic effects. Therefore,in situ MWA combined with immunotherapy provides an alternative treatment method for patients who have trouble due to their insensitivity to chemotherapy.
Objective To perform a preclinical test of a delineation software based on atlas-based auto-segmentation (ABAS), to evaluate its accuracy in the delineation of organs at risk (OARs) in radiotherapy planning for nasopharyngeal carcinoma (NPC), and to provide a basis for its clinical application. Methods Using OARs manually contoured by physicians on planning-CT images of 22 patients with NPC as the standard, the automatic delineation using two different algorithms (general and head/neck) of the ABAS software were applied to the following tests:(1) to evaluate the restoration of the atlas by the software, automatic delineation was performed on copied images from each patient using the contours of OARs manually delineated on the original images as atlases;(2) to evaluate the accuracy of automatic delineation on images from various patients using a single atlas, the contours manually delineated on images from one patients were used as atlases for automatic delineation of OARs on images from other patients. Dice similarity coefficient (DSC), volume difference (Vdiff), correlation between the DSC and the volume of OARs, and efficiency difference between manual delineation and automatic delineation plus manual modification were used as indices for evaluation. Wilcoxon signed rank test and Spearman correlation analysis were used. Results The head/neck algorithm had superior restoration of the atlas over the general algorithm. The DSC was positively correlated with the volume of OARs and was higher than 0.8 for OARs larger than 1 cc in volume in the restoration test. For automatic delineation with the head/neck algorithm using a single atlas, the mean DSC and Vdiff were 0.81-0.90 and 2.73%-16.02%, respectively, for the brain stem, temporal lobes, parotids, and mandible, while the mean DSC was 0.45-0.49 for the temporomandibular joint and optic chiasm. Compared with manual delineation, automatic delineation plus manual modification saved 68% of the time. Conclusions A preclinical test is able to determine the accuracy and conditions of the ABAS software in specific clinical application. The tested software can help to improve the efficiency of OAR delineation in radiotherapy planning for NPC. However, it is not suitable for delineation of OAR with a relatively small volume.
Objective To construct the uniform electron density couch model (model A ED=0.25) and two components non uniform electron density couch model (model B FD=0.5and foam core=0.1) in the Monaco treatment planning system for theiBEAM evo Extension 415,and to compare which model can better quantify the treatment couch influence on radiation dose. Methods Phantom was positioned in the center of the couch,the attenuation of the couch was evaluated with 6 MV for a field size of 10 cm×10 cm. Dose measurements of couch attenuation were performed at gantry angles from 180.0° to 122.8°,using a 0.125cc semiflex ionization chamber (PTW),isocentrically placed in the center of a homogeneous cylindrical phantom. Each experimental setup was first measured on the linear accelerator and then reproduced in the TPS.By adjusting the relative-to water electron density (ED) values of the couch,the measured attenuation was replicated. The model accuracies of the model A and model B were evaluated by comparing the measured and calculated results at the minimum computational grid (2 mm) and maximum computing grid (5 mm),respectively. Results The maximum measured and calculated percentage deviation for the central phantom position was 4.01%.The couch model was included in the TPS with a uniform ED of 0.25 or a 2 component model with a fiber ED=0.5 and foam core ED=0.1.For model A and B under 2 and 5 mm voxel grid size,the mean absorbed dose with couch was reduced to 0.61%,0.84%,0.71% and 0.92% from 2.8% without couch. Conclusions Model A has a good agreement between measured and calculated dose distributions for all different voxel grid sizes and gantry angles. It can accurately describes the dose perturbations due to the presence of the couch and should therefore be used during treatment planning.
Objective To observe myocardial tolerance to ischemia/reperfusion (I/R) injury in rats after exposure to X-ray irradiation. Methods Twelve male rats were randomly divided into control group and radiation group. The rat model of radiation-induced heart disease was established in the radiation group by precordial irradiation with 20.0 Gy of 6 MV X-ray in a single fraction. At 14 days after model establishment, the Langendorff perfusion technique was performed in the two groups and the cardiac parameters including left ventricular developing pressure (LVDP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure rise/fall (+/-LVdp/dtmax), and coronary flow (CF) were recorded. Myocardial infarct size after I/R was compared between the two groups by 2,3,5-triphenyltetrazolium chloride staining. Results After 30 minutes of ischemia and 60 minutes of reperfusion, the irradiation group had a significantly slower CF than the control group (5.64±0.35 vs. 8.38±0.52 ml/min, P=0.002). Moreover, the irradiation group had substantially poorer recovery of cardiac function in isolated hearts compared with the control group, as shown by a significantly reduced LVDP (25.4±2.31 vs. 52.76±2.76 mm Hg(1 mm Hg=0.133 kPa), P=0.000), significantly reduced+/-LVdp/dtmax (547.04±78.74 vs. 1 100.05±83.35 mm Hg(1 mm Hg=0.133 kPa)/s,P=0.001;-408.81±56.74 vs-813.62±73.82 mm Hg(1 mm Hg=0.133 kPa)/s, P=0.002), and a significantly increased LVEDP (85.29±4.61 vs. 65.65±3.65 mm Hg(1 mm Hg=0.133 kPa), P=0.012). X-ray irradiation induced a significantly increased percentage of myocardial infarct size in rats (44.67%±0.95% vs. 30.46%±0.96%,P=0.000). Conclusions X-ray irradiation can induce coronary injury, reduce myocardial tolerance to I/R injury, and increase myocardial infarct size after I/R in rats.
Objective To investigate DNA double-strand breaks and radiosensitization in renalcarcinoma 786-O cells induced by fludarabine (FA) combined with different ionizing radiations. Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation. Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle. The neutral comet assay was used to detect DNA double-strand breaks. The colony-forming assay was used to evaluate the effects of different treatments on cell survival. Comparison between groups was made by one-way analysis of variance or Dunnet’s t test. Results Compared with FA alone or irradiation alone, FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX (P=0.007,0.001);FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase (P=0.000,0.000);the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage (P=0.020,0.060);FA significantly reduced the colony-forming rate after irradiation (P=0.000,0.030;0.001,0.040). Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties. Particularly, FA substantially enhances the cell death induced by heavy ion beam irradiation.
Objective To study the individual and combined effects of HER-2 and TOP2A on the radiosensitivity of breast cancer SK-Br-3 cells, and to provide a basis for clinical research. Methods To knock down the expression of HER-2 and TOP2A, the recombinant plasmids expressing HER-2 siRNA or/and TOP2A siRNA were constructed and used to transfect SK-Br-3 cells using Lipofectamine 2000. Western blot was used to evaluate the knockdown efficiency two days later. Flow cytometry and MTT assay were used to evaluate apoptosis and proliferation in cells exposed to radiation, respectively. The expression of apoptosis-and proliferation-related proteins, consisting of caspase-3, Bcl-2, and Ki-67, was determined. The colony-formation assay was used to measure radiosensitivity. Results The breast cancer SK-Br-3 cells with HER-2 or TOP2A knockdown had a higher apoptosis rate and a lower proliferation rate after exposure to radiation. The apoptotic marker, activated caspase-3, had elevated expression, while the anti-apoptotic protein Bcl-2 and the proliferation marker Ki-67 had reduced expression. Knockdown of both HER-2 and TOP2A further promoted apoptosis and inhibited proliferation and colony formation, indicating a synergistic effect of HER-2 and TOP2A. Conclusions Knockdown of HER-2 and TOP2A expression elevates the radiosensitivity and apoptosis rate, and reduces the proliferation rate and colony-formation rate in the breast cancer SK-Br-3 cells. Moreover, there is a synergistic effect between HER-2 and TOP2A. The mechanism is probably related to the proliferation-related protein Ki-67 and the apoptosis pathway involving caspase-3 and Bcl-2.
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