Computer-assisted ultrasound assessment of plaque characteristics in radiation-induced and non-radiation-induced carotid atherosclerosis.

BACKGROUND: This study investigated the feasibility of using a computer-assisted method to evaluate and differentiate the carotid plaque characteristics in radiation-induced and non-radiation-induced carotid atherosclerosis. METHODS: This study included 107 post-radiotherapy (post-RT) nasopharyngeal carcinoma (NPC) patients and 110 subjects with cardiovascular risk factors (CVRFs). Each participant had a carotid ultrasound examination, and carotid plaques and carotid intima-media thickness (CIMT) were evaluated with grey scale ultrasound. The carotid plaque characteristics were evaluated for grey-scale median (GSM) and detailed plaque texture analysis (DPTA) using specific computer software. In DPTA, five different intra-plaque components were colour-coded according to different grey scale ranges. A multivariate linear regression model was used to evaluate the correlation of risk factors and carotid plaque characteristics. RESULTS: Post-RT NPC patients have significantly higher CIMT (748±15.1 µm, P=0.001), more patients had a plaque formation (80.4%, P<0.001) and more plaque locations (2.3±0.2, P<0.001) than CVRF subjects (680.4±10.0 µm, 38.2% and 0.5±0.1 respectively). Among the five intra-plaque components, radiation-induced carotid plaques had significantly larger area of calcification (4.8%±7.7%, P=0.012), but lesser area of lipid (42.1%±16.9%, P=0.034) when compared to non-radiation-induced carotid plaques (3.0%±5.7% and 46.3%±17.9% respectively). Age, radiation and number of CVRF were significantly associated with the carotid atherosclerosis burden (P<0.001). Besides, age was significantly associated with the amount of lipid and calcification within carotid plaques (P<0.001). CONCLUSIONS: Radiation caused more severe carotid artery disease than CVRF with larger CIMT and more prevalent of carotid plaque. Radiation-induced carotid plaques tended to have more intra-plaque calcifications, whereas non-radiation-induced carotid plaques had more lipids. Ultrasound aided by computer-assisted image analysis has potential for more accurate assessment of carotid atherosclerosis.

Comparison of the verification performance and radiation dose between ExacTrac x-ray system and On-Board Imager-A phantom study.

Recently, On-Board Imager (OBI) and ExacTrac x-ray 6 degree-of-freedom system (ExacTrac) are increasingly used verification systems in local radiotherapy centers. This study aimed to compare the differences between these two systems in terms of verification accuracy, organ doses, and verification time for head-and-neck (H&N) and pelvic cases. Rando anthropomorphic phantoms of H&N and pelvic regions were positioned with known set-up deviations from the reference position in the linear accelerator. x-Ray verification images were then acquired using both systems. Verification accuracy was evaluated based on the residual positioning error (δD) after image registration. Thermoluminescence dose meters (TLD-100s) were placed in specific locations of the phantoms for the measurement of imaging doses at the organs of interest. Besides, the verification time was also recorded for comparison. Most average detection errors for both systems were within 1 mm. The detection error of ExacTrac was significantly larger than OBI in the H&N region in all directions (p < 0.05), but was significantly lower in the pelvis (p < 0.05). The mean imaging doses to all organs of interest from ExacTrac were significantly lower than OBI (p < 0.05). The mean verification time for ExacTrac was about 10 seconds, which was significantly shorter than the 100 seconds in OBI (p < 0.001). Both verification systems achieved satisfactory performance in the H&N and pelvic regions despite ExacTrac being better in terms of verification time and organ dose. The verification accuracy of Exactrac was better in pelvic region than the H&N region when compared with OBI.

Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy.

OBJECTIVES: Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose. METHODS: Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated. RESULTS: The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05). CONCLUSION: The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.

Vector-model-supported optimization in volumetric-modulated arc stereotactic radiotherapy planning for brain metastasis.

Long planning time in volumetric-modulated arc stereotactic radiotherapy (VMA-SRT) cases can limit its clinical efficiency and use. A vector model could retrieve previously successful radiotherapy cases that share various common anatomic features with the current case. The prsent study aimed to develop a vector model that could reduce planning time by applying the optimization parameters from those retrieved reference cases. Thirty-six VMA-SRT cases of brain metastasis (gender, male [n = 23], female [n = 13]; age range, 32 to 81 years old) were collected and used as a reference database. Another 10 VMA-SRT cases were planned with both conventional optimization and vector-model-supported optimization, following the oncologists' clinical dose prescriptions. Planning time and plan quality measures were compared using the 2-sided paired Wilcoxon signed rank test with a significance level of 0.05, with positive false discovery rate (pFDR) of less than 0.05. With vector-model-supported optimization, there was a significant reduction in the median planning time, a 40% reduction from 3.7 to 2.2 hours (p = 0.002, pFDR = 0.032), and for the number of iterations, a 30% reduction from 8.5 to 6.0 (p = 0.006, pFDR = 0.047). The quality of plans from both approaches was comparable. From these preliminary results, vector-model-supported optimization can expedite the optimization of VMA-SRT for brain metastasis while maintaining plan quality.

Vector-model-supported approach in prostate plan optimization.

Lengthy time consumed in traditional manual plan optimization can limit the use of step-and-shoot intensity-modulated radiotherapy/volumetric-modulated radiotherapy (S&S IMRT/VMAT). A vector model base, retrieving similar radiotherapy cases, was developed with respect to the structural and physiologic features extracted from the Digital Imaging and Communications in Medicine (DICOM) files. Planning parameters were retrieved from the selected similar reference case and applied to the test case to bypass the gradual adjustment of planning parameters. Therefore, the planning time spent on the traditional trial-and-error manual optimization approach in the beginning of optimization could be reduced. Each S&S IMRT/VMAT prostate reference database comprised 100 previously treated cases. Prostate cases were replanned with both traditional optimization and vector-model-supported optimization based on the oncologists' clinical dose prescriptions. A total of 360 plans, which consisted of 30 cases of S&S IMRT, 30 cases of 1-arc VMAT, and 30 cases of 2-arc VMAT plans including first optimization and final optimization with/without vector-model-supported optimization, were compared using the 2-sided t-test and paired Wilcoxon signed rank test, with a significance level of 0.05 and a false discovery rate of less than 0.05. For S&S IMRT, 1-arc VMAT, and 2-arc VMAT prostate plans, there was a significant reduction in the planning time and iteration with vector-model-supported optimization by almost 50%. When the first optimization plans were compared, 2-arc VMAT prostate plans had better plan quality than 1-arc VMAT plans. The volume receiving 35 Gy in the femoral head for 2-arc VMAT plans was reduced with the vector-model-supported optimization compared with the traditional manual optimization approach. Otherwise, the quality of plans from both approaches was comparable. Vector-model-supported optimization was shown to offer much shortened planning time and iteration number without compromising the plan quality.

Influence of autophagy on the efficacy of radiotherapy.

Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed.

Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation-induced fibrosis in patients with nasopharyngeal carcinoma.

Radiation-induced fibrosis is one of the late complications of radiotherapy (RT) for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the association between X-ray repair cross-complementing protein 1 and 3 (XRCC1 and XRCC3, respectively) gene haplotypes and radiation-induced fibrosis in NPC patients. Genomic DNA was extracted from blood samples of 120 NPC patients previously treated with RT. In total, 12 tag single-nucleotide polymorphisms (SNPs) were selected from the XRCC1 and XRCC3 genes and were genotyped using restriction fragment length polymorphism analysis or unlabeled probe melting analysis. Single-marker and haplotype analyses were performed using multivariate logistic regression analysis. The functional variant rs861539 of XRCC3 may be associated with radiation-induced fibrosis [asymptotic P-value (Pasym)<0.05]. No significant association was observed between radiation-induced fibrosis and any of the tag SNPs of XRCC1 and XRCC3 in either single-marker or haplotype analysis after 10,000 permutations [empirical P-value (Pemp)>0.05]. Our preliminary results indicated that the rs861539 variant of XRCC3 may be associated with an increased risk of radiation-induced fibrosis; however, a large-scale study is required to confirm this result.

Developing an adaptive radiation therapy strategy for nasopharyngeal carcinoma.

Adaptive radiotherapy (ART) has recently been introduced to restore the planned dose distribution by accounting for the anatomic changes during treatment. By quantifying the anatomic changes in nasopharyngeal carcinoma (NPC) patients, this study aimed to establish an ART strategy for NPC cases. A total of 30 NPC patients treated with helical tomotherapy were recruited. In the pretreatment megavoltage CT images, the anatomic changes of the posterolateral wall of nasopharynx (P-NP), neck region and parotid glands were measured and assessed. One-way repeated measure ANOVA was employed to define threshold(s) at any time-point. The presence of a threshold(s) would indicate significant anatomical change(s) such that replanning should be suggested. A pragmatic schedule for ART was established by evaluating the threshold for each parameter. Results showed the P-NP, parotid gland and neck volumes demonstrated significant regressions over time. Respectively, the mean loss rates were 0.99, 1.35, and 0.39 %/day, and the mean volume losses were 35.70, 47.54 and 11.91% (all P < 0.001). The parotid gland shifted medially and superiorly over time by a mean of 0.34 and 0.24 cm, respectively (all P < 0.001). The neck region showed non-rigid posterior displacement, which increased from upper to lower neck. According to the threshold occurrences, three replans at 9th, 19th and 29th fractions were proposed. This ART strategy was able to accommodate the dosimetric consequences due to anatomic deviation over the treatment course. It is clinically feasible and would be recommended for centers where an adaptive planning system was not yet available.

Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma.

PURPOSE: Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples. METHODS: cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared. RESULTS: The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC. CONCLUSION: Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.

Development of a prototype of the tele-localisation system in radiotherapy using personal digital assistant via wireless communication.

In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele-localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele-localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi-Fi network; a PDA (oncologist's site) installed with the custom-built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5 min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele-localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele-localisation procedure with reasonable speed and accuracy.

Dosimetric evaluation of a three-phase adaptive radiotherapy for nasopharyngeal carcinoma using helical tomotherapy.

Adaptive radiotherapy (ART) has been introduced to correct the radiation-induced anatomic changes in head and neck cases during a treatment course. This study evaluated the potential dosimetric benefits of applying a 3-phase adaptive radiotherapy protocol in nasopharyngeal carcinoma (NPC) patients compared with the nonadaptive single-phase treatment protocol. Ten NPC patients previously treated with this 3-phase radiation protocol using Hi-Art Tomotherapy were recruited. Two new plans, PII-ART and PIII-ART, were generated based on the up-to-date computed tomography (CT) images and contours and were used for treatment in phase two (PII; after 25th fraction) and phase three (PIII; after 35th fraction), respectively. To simulate the situation of no replanning, 2 hybrid plans denoted as PII-NART and PIII-NART were generated using the original contours pasted on the PII- and PIII-CT sets by CT-CT fusion. Dosimetric comparisons were made between the NART plans and the corresponding ART plans. In both PII- and PIII-NART plans, the doses to 95% of all the target volumes (D95) were increased with better dose uniformity, whereas the organs at risk (OARs) received higher doses compared with the corresponding ART plans. Without replanning, the total dose to 1% of brainstem and spinal cord (D1) significantly increased 7.87 ± 7.26% and 10.69 ± 6.72%, respectively (P = 0.011 and 0.001, respectively), in which 3 patients would have these structures overdosed when compared with those with two replannings. The total maximum doses to the optic chiasm and pituitary gland and the mean doses to the left and right parotid glands were increased by 10.50 ± 10.51%, 8.59 ± 6.10%, 3.03 ± 4.48%, and 2.24 ± 3.11%, respectively (P = 0.014, 0.003, 0.053, and 0.046, respectively). The 3-phase radiotherapy protocol showed improved dosimetric results to the critical structures while keeping satisfactory target dose coverage, which demonstrated the advantages of ART in helical tomotherapy of NPC.

Dosimetric comparison of intensity-modulated stereotactic radiotherapy with other stereotactic techniques for locally recurrent nasopharyngeal carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. METHODS AND MATERIALS: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrieved from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. RESULTS: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. CONCLUSION: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.

A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma.

BACKGROUND: Radiation-induced thyroid disorders have been reported in radiotherapy of head and neck cancers. This study evaluated the radiation-induced damages to thyroid gland in patients with nasopharyngeal carcinoma (NPC). METHODS: Forty-five patients with NPC treated by radiotherapy underwent baseline thyroid hormones (free triiodothyronine, free thyroxine [fT4], and thyrotropin [TSH]) examination and CT scan before radiotherapy. The volume of the thyroid gland was calculated by delineating the structure in the corresponding CT slices using the radiotherapy treatment planning system. The thyroid doses were estimated using the treatment planning system. Subsequent CT scans were conducted at 6, 12, and 18 months after radiotherapy, whereas the hormone levels were assessed at 3, 6, 12, and 18 months after radiotherapy. Trend lines of the volume and hormone level changes against time were plotted. The relationship between the dose and the change of thyroid volume and hormone levels were evaluated using the Pearson correlation test. RESULTS: An average of 20% thyroid volume reduction in the first 6 months and a further 8% shrinkage at 12 months after radiotherapy were observed. The volume reduction was dependent on the mean thyroid doses at 6, 12, and 18 months after radiotherapy (r = -0.399, -0.472, and -0.417, respectively). Serum free triiodothyronine and fT4 levels showed mild changes of <2.5% at 6 months, started to drop by 8.8% and 11.3%, respectively, at 12 months, and became stable at 18 months. The mean serum TSH level increased mildly at 6 months after radiotherapy and more steeply after 18 months. At 18 months after radiotherapy, 12 patients had primary hypothyroidism with an elevated serum TSH, in which 4 of them also presented with low serum fT4. There was a significant difference (p = 0.014) in the mean thyroid doses between patients with hypothyroidism and normal thyroid function. CONCLUSIONS: Radiotherapy for patients with NPC caused radiation-induced changes of the thyroid gland. The shrinkage of the gland was greatest in the first 6 months after radiotherapy, whereas the serum fT4 and TSH levels changed at 12 months. Radiation-induced changes were dependent on the mean dose to the gland. Therefore, measures to reduce the thyroid dose in radiotherapy should be considered.