Vincent W.C. Wu

Assessment of post-radiotherapy salivary glands

Salivary glands are usually irradiated during radiotherapy for head and neck cancers, which can lead to radiation-induced damage. Radiation-induced xerostomia (oral dryness) is the most common post-radiotherapy complication for head and neck cancer patients and can reduce the patients quality of life. Accurate and efficient salivary gland assessment methods provide a better understanding of the cause and degree of xerostomia, and may help in patient management. At present, there are different methods for the assessment of salivary gland hypofunction; however, none of them are considered to be standard procedure. This article reviews the value of common methods in the assessment of post-radiotherapy salivary glands.

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.

A prospective study on volumetric and dosimetric changes during intensity-modulated radiotherapy for nasopharyngeal carcinoma patients.

BACKGROUND AND PURPOSE Significant tumor shrinkage and weight loss may occur during Intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aims to evaluate the dosimetric effect of volumetric changes on target volumes and organs at risk (OARs) during IMRT, using reassessment of computed tomography (CT) and magnetic resonance imaging (MRI). MATERIAL AND METHODS Nineteen loco-regionally advanced NPC patients treated with IMRT were recruited prospectively. Repeat planning CT and MRI were acquired at 30 and 50 Gy intervals. Recontouring of target volumes and OARs was based on the fused CT-MRI images. Hybrid plans with recontouring were generated. The assessment of volumetric and dosimetric changes was performed by comparing the hybrid plans with the original plan. RESULTS There was volume reduction of target volumes and parotid glands over the course of IMRT. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to most of target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher median doses to the parotid glands. CONCLUSIONS Replanning with repeat CT and MRI scans at 30 Gy is essential to keep a satisfactory dose to the target volumes and avoid overdosing the OARs.

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.

Evaluation of the influence of tumor location and size on the difference of dose calculation between Ray Tracing algorithm and Fast Monte Carlo algorithm in stereotactic body radiotherapy of non-small cell lung cancer using CyberKnife

This study evaluated the extent of improvement in dose predication accuracy achieved by the Fast Monte Carlo algorithm (MC) compared to the Ray Tracing algorithm (RAT) in stereotactic body radiotherapy (SBRT) of non‐small cell lung cancer (NSCLC), and how their differences were influenced by the tumor site and size. Thirty‐three NSCLC patients treated with SBRT by CyberKnife in 2011 were recruited. They were divided into the central target group (n=17) and peripheral target group (n=16) according to the RTOG 0236 guidelines. Each group was further divided into the large and small target subgroups. After the computation of treatment plans using RAT, a MC plan was generated using the same patient data and treatment parameters. Apart from the target reference point dose measurements, various dose parameters for the planning target volume (PTV) and organs at risk (OARs) were assessed. In addition, the “Fractional Deviation” (FDev) was also calculated for comparison, which was defined as the ratio of the RAT and MC values. For peripheral lung cases, RAT produced significantly higher dose values in all the reference points than MC. The FDev of all reference point doses and dose parameters was greater in the small target than the large target subgroup. For central lung cases, there was no significant reference point and OAR dose differences between RAT and MC. When comparing between the small target and large target subgroups, the FDev values of all the dose parameters and reference point doses did not show significant difference. Despite the shorter computation time, RAT was inferior to MC, in which the target dose was usually overestimated. RAT would not be recommended for SBRT of peripheral lung tumors regardless of the target size. However, it could be considered for large central lung tumors because its performance was comparable to MC. PACS number: 87

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.

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.

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.

Longitudinal study on the correlations of thyroid antibody and thyroid hormone levels after radiotherapy in patients with nasopharyngeal carcinoma with radiation-induced hypothyroidism

The purpose of this study was to evaluate the correlations of thyroid antibody and thyroid hormone in postradiotherapy (post‐RT) patients with nasopharyngeal carcinoma (NPC).

Technologies of Image Guidance and the Development of Advanced Linear Accelerator Systems for Radiotherapy

As advanced radiotherapy approaches for targeting the tumor and sparing the normal tissues have been developed, the image guidance of therapy has become essential to directing and confirming treatment accuracy. To approach these goals, image guidance devices now include kV on-board imagers, kV/MV cone-beam CT systems, CT-on-rails, and mobile and in-room radiographic/fluoroscopic systems. Nonionizing sources, such as ultrasound and optical systems, and electromagnetic devices have been introduced to monitor or track the patient and/or tumor positions during treatment. In addition, devices have been designed specifically for monitoring and/or controlling respiratory motion. Optimally, image-guided radiation therapy systems should possess 3 essential elements: (1) 3D imaging of soft tissues and tumors, (2) efficient acquisition and comparison of the 3D images, and (3) an efficacious process for clinically meaningful intervention. Understanding and using these tools effectively is central to current radiotherapy practice. The implementation and integration of these devices continue to carry practical challenges, which emphasize the need for further development of the technologies and their clinical applications.