Clinical Evaluation of Fiducial Marker Pre-Planning for Virtual Bronchoscopic Navigation Implantation in Lung Tumour Patients Treated With CyberKnife.

Purpose: For the treatment of invisible lung tumours with CyberKnife (CK), fiducial markers (FMs) were implanted as an internal surrogate under virtual bronchoscopic navigation (VBN). This research aims to study the benefits of introducing an additional procedure in assigning the optimal FM positions using a pre-procedure planning system and performing virtual simulation before implantation. The objectives were 1) to reduce the duration of the FM implantation procedure, 2) to reduce the radiation exposure in dose area product (DAP) (dGy*cm2) to patients, and 3) to increase the number of FMs implanted around the tumour. Methods and Materials: This study is retrospective, single-centre, and observational in nature. A total of 32 patients were divided into two groups. In Group 1, 18 patients underwent conventional VBN FM implantation. In Group 2, 14 patients underwent additional pre-procedure planning and simulation. The steps of pre-procedure planning include 1) importing CT images into the treatment planning system (Eclipse, Varian Medical Systems, Inc.) and delineating five to six FMs in their ideal virtual positions and 2) copying the FM configuration into VBN planning software (LungPoint Bronchus Medical, Inc.) for verification and simulation. Finally, the verified FMs were deployed through VBN with the guidance of the LungPoint planning software. Results: A total of 162 FMs were implanted among 35 lesions in 32 patients aged from 37 to 92 (median = 66; 16 men and 16 women). Results showed that 1) the average FM insertion time was shortened from 41 min (SD = 2.05) to 23 min (SD = 1.25), p = 0.00; 2) the average absorbed dose of patients in DAP was decreased from 67.4 cGy*cm2 (SD = 14.48) to 25.3 cGy*cm2 (SD = 3.82), p = 0.01 (1-tailed); and 3) the average number of FMs implanted around the tumour was increased from 4.7 (SD = 0.84) to 5.6 (SD = 0.76), p = 0.00 (1-tailed). Conclusion: Pre-procedure planning reduces the FM implantation duration from 41.1 to 22.9 min, reduces the radiation exposure in DAP from 67.4 to 25.3 dGy*cm2, and increases the number of FMs inserted around the tumour from 4.7 to 5.6.

Respiratory 4D-Gating F-18 FDG PET/CT Scan for Liver Malignancies: Feasibility in Liver Cancer Patient and Tumor Quantitative Analysis.

PURPOSE: To evaluate the potential clinical role and effectiveness of respiratory 4D-gating F-18 FDG PET/CT scan for liver malignancies, relative to routine (3D) F-18 FDG PET/CT scan. MATERIALS AND METHODS: This study presented a prospective clinical study of 16 patients who received F-18 FDG PET/CT scan for known or suspected malignant liver lesions. Ethics approvals were obtained from the ethics committees of the Hong Kong Baptist Hospital and The Hong Kong Polytechnic University. Liver lesions were compared between the gated and ungated image sets, in terms of 1) volume measurement of PET image, 2) accuracy of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and 3) accuracy of total lesion glycoses (TLG). Statistical analysis was performed by using a two-tailed paired Student t-test and Pearson correlation test. RESULTS: The study population consisted of 16 patients (9 males and 7 females; mean age of 65) with a total number of 89 lesions. The SUVmax and SUVmean measurement of the gated PET images was more accurate than that of the ungated PET images, compared to the static reference images. An average of 21.48% (p < 0.001) reduction of the tumor volume was also observed. The SUVmax and SUVmean of the gated PET images were improved by 19.81% (p < 0.001) and 25.53% (p < 0.001), compared to the ungated PET images. CONCLUSIONS: We have demonstrated the feasibility of implementing 4D PET/CT scan for liver malignancies in a prospective clinical study. The 4D PET/CT scan for liver malignancies could improve the quality of PET image by improving the SUV accuracy of the lesions and reducing image blurring. The improved accuracy in the classification and identification of liver tumors with 4D PET image would potentially lead to its increased utilization in target delineation of GTV, ITV, and PTV for liver radiotherapy treatment planning in the future.

Comparison of dosimetric impact of intra-fractional setup discrepancy between multiple- and single-isocenter approaches in linac-based stereotactic radiotherapy of multiple brain metastases.

INTRODUCTION: Treatment of multiple brain metastases by linac-based stereotactic radiotherapy (SRT) can employ either a multiple-isocenter (MI) or single-isocenter (SI) approach. The purposes of this study were to evaluate the dosimetric results of MI and SI approaches and compare the impacts of intra-fractional setup discrepancies on the robustness of respective approaches using isocenter shifts, whether the same magnitude of translational and rotational effects could lead to a significant difference between the two approaches. METHODS: Twenty-two patients with multiple brain metastases treated by linac-based SRT were recruited. Treatment plans were computed with both the MI and SI approaches. For the MI approach, the isocenter was located at the geometric center of each planning target volumes (PTVs), whereas the isocenter of the SI approach was located midway between the PTV centroids. To simulate the intra-fractional errors, isocenter displacements including translational and rotational shifts were hypothetically applied. Apart from the dosimetric outcomes of the two approaches, the impact of the isocenter shifts on PTVs and organs at risk (OARs) were recorded in terms of the differences (δ) in dose parameters relative to the reference plan and was then compared between the MI and SI approaches. RESULTS: Both MI and SI plans met the plan acceptance criteria. The mean Paddick conformity index (Paddick CI) and Dmax of most OARs between MI and SI plans did not show a significant difference, except that higher doses to the left optic nerve and optic chiasm were found in SI plans (p = 0.03). After the application of the isocenter shifts, δCI increased with an increase in the magnitude of the isocenter shift. When comparing between MI and SI plans, the δCIs were similar (p > 0.05) for all extents of translational shifts, but δCIs were significantly higher in SI plans after application of all rotations particularly ±1.5° and ±2.0° shifts. Despite the result that the majority of δDMax of OARs were higher in the SI plans, only the differences in the left optic nerve and chiasm showed generally consistent significance after both translational ≥±1 mm and rotational shifts of ≥±1 ∘ $^\circ $ . CONCLUSION: Both MI and SI approaches could produce clinically acceptable plans. However, isocenter shifts brought dosimetric impacts to both MI and SI approaches and the effects increased with the increase of the shift magnitude. Although similar impacts were shown in plans of both approaches after translational isocenter shift, SI plans were relatively more vulnerable than MI plans to rotational shifts.

A longitudinal study on parotid and submandibular gland changes assessed by magnetic resonance imaging and ultrasonography in post-radiotherapy nasopharyngeal cancer patients.

OBJECTIVES: With regard to the intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, this longitudinal study evaluated the radiation-induced changes in the parotid and submandibular glands in terms of gland size, echogenicity and haemodynamic parameters. METHODS: 21 NPC patients treated by IMRT underwent MRI and ultrasound scans before radiotherapy, and at 6, 12, 18 and 24 months after treatment. Parotid and submandibular gland volumes were measured from the MRI images, whereas the parotid echogenicity and haemodynamic parameters including the resistive index, pulsatility index, peak systolic velocity and end diastolic velocity were evaluated by ultrasonography. Trend lines were plotted to show the pattern of changes. The correlations of gland doses and the post-RT changes were also studied. RESULTS: The volume of the parotid and submandibular glands demonstrated a significant drop from pre-RT to 6 months post-RT. The parotid gland changed from hyperechoic before RT to either isoechoic or hypoechoic after treatment. The resistive index and pulsatility index decreased from pre-RT to 6 month post-RT, then started to increase at 12 month time interval. Both peak systolic velocity and end diastolic velocity increased after 6 months post-RT then followed a decreasing trend up to 24 months post-RT. There was mild correlation between post-RT gland dose and gland volume, but not with haemodynamic changes. CONCLUSIONS: Radiation from IMRT caused shrinkage of parotid and submandibular glands in NPC patients. It also changed the echogenicity and vascular condition of the parotid gland. The most significant changes were observed at 6 months after radiotherapy. ADVANCES IN KNOWLEDGE: It is the first paper that reports on the longitudinal changes of salivary gland volume, echogenicity and haemodynamic parameters altogether in NPC patients after radiotherapy. The results are useful for the prediction of glandular changes that is associated with xerostomia, which help to provide timely management of the complication when the patients attend follow-up visits.

Radiation induced temporal lobe necrosis in nasopharyngeal cancer patients after radical external beam radiotherapy.

Radiation-induced temporal lobe necrosis (TLN) is one of the late post-radiotherapy complications in nasopharyngeal cancer (NPC) patients. Since NPC is common to have skull base infiltration, irradiation of the temporal lobes is inevitable despite the use of the more advanced intensity-modulated radiotherapy (IMRT). Moreover, the diagnosis and treatment of TLN remain challenging. In this review, we discuss the diagnosis of TLN with conventional and advanced imaging modalities, onset and predictive parameters of TLN development, the impact of IMRT on TLN in terms of incidence and dosimetric analyzes, and the recent advancements in the treatment of TLN.

Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond.

Metastasis is the main cause of cancer-related mortality. Although the actual process of metastasis remains largely elusive, epithelial-mesenchymal transition (EMT) has been considered as a major event in metastasis. Besides, hypoxia is common in solid cancers and has been considered as an important factor for adverse treatment outcomes including metastasis. Since EMT and hypoxia potentially share several signaling pathways, many recent studies focused on investigate the issue of hypoxia-induced EMT. Among all potential mediators of hypoxia-induced EMT, hypoxia-inducible factor-1α (HIF-1α) has been studied extensively. Moreover, there are other potential mediators that may also contribute to the process. This review aims to summarize the recent reports on hypoxia-induced EMT by HIF-1α or other potential mediators and provide insights for further investigations on this issue. Ultimately, better understanding of hypoxia-induced EMT may allow us to develop anti-metastatic strategies and improve treatment outcomes.

JNK Pathway Mediates Low Oxygen Level Induced Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer Cells.

(1) Background: Epithelial-mesenchymal transition (EMT) and cancer cell stemness maintenance (SM) are important factors for cancer metastasis. Although hypoxia has been considered as a possible factor for EMT induction and promotion of SM, studies in this area, apart from hypoxia-inducible factor (HIF) pathways and severe hypoxia, are scant. This study aimed to evaluate the effects of different oxygen levels on EMT induction and SM and elucidate the signaling pathways involved in colorectal cancer cells. (2) Methods: Cell morphological analysis, migration assay, immunofluorescence staining of cytoskeleton and Western blotting were performed on human colorectal cancer cells HT-29, DLD-1, and SW-480 cultured at 1%, 10%, and normal (21%) O2 levels. The role played by c-Jun N-terminal kinase (JNK) was evaluated through the use of the specific JNK inhibitor SP600125. (3) Results: This study evaluated 1% and 10% O2 are possible conditions for EMT induction and SM. This study also demonstrated the partial relieve of EMT induction and SM by SP600125, showing the importance of the JNK pathway in these processes. Furthermore, this study proposed a novel pathway on the regulation of Akt by JNK-c-Jun. (4) Conclusions: This study suggests 10% O2 as another possible condition for EMT induction, and SM and JNK pathways play important roles in these processes through multiple factors. Inhibition of JNK could be explored as treatment for inhibiting metastasis in colorectal cancer cells.

A Review on the Assessment of Radiation Induced Salivary Gland Damage After Radiotherapy.

Head and neck cancers are common in Southern China including Hong Kong. Intensity modulated radiotherapy has been the treatment of choice for these patients. Although radiotherapy provides good local control, radiotherapy treatment side-effects are still inevitable due to close proximity of the organs at risk from the target volume. Xerostomia, which is caused due to the damage of salivary glands, is one of the main radiation induced toxicities in post-radiotherapy head and neck patients. This review article discusses the methods for the assessing of radiation induced salivary gland changes including the gland morphology and saliva flow rate. The discussion also includes the recovery of the salivary gland after radiotherapy and how it is affected by the dose. It is expected that the future direction in monitoring the recovery of salivary glands will focus in cellular or molecular levels, and the development of imaging biomarker.

A dosimetric comparison of the use of equally spaced beam (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in head and neck cancers treated by intensity modulated radiotherapy.

INTRODUCTION: Previous studies have shown that the beam arrangement had significant influence on plan quality in intensity modulated radiotherapy (IMRT). This study aimed to evaluate the dosimetric performance of beam arrangement methods by employing equally spaced beams (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in the planning of five types of head and neck (H&N) cancers treated by IMRT. METHODS: Five plans of different beam arrangement methods were optimized for 119 H&N cancer patients with the prescription of 66-70 Gy for high-risk planning target volume (PTV), 60 Gy for intermediate risk PTV, 54 Gy for low-risk PTV using a simultaneously integrated boost method. The five-beam arrangement methods were: ESB, coplanar BAO (BAOc), noncoplanar BAO (BAOnc), two-arc VMAT (VMAT2), and three-arc VMAT (VMAT3). The H&N cancers included cancers of nasopharynx, oral cavity, larynx, maxillary sinus, and parotid. Although the partial arc VMAT could be used in cases where the PTVs were situated at one side of the head such as the parotid, this arrangement was not included because it was intended to include only the beam arrangements that were applicable to all the types of head and neck cancers in the study. The plans were evaluated using a "figure-of-merit" known as uncomplicated target conformity index (UTCI). In addition, PTV conformation number and homogeneity index, normal tissue integral dose, and organ at risk (OAR) doses were also used. The mean values of these parameters were compared among the five plans. RESULTS: All treatment plans met the preset dose requirements for the target volumes and OARs. For nasopharyngeal cancer, VMAT3 and BAOnc demonstrated significantly higher UTCI. For cancer of oral cavity, most beam arrangement showed similar UTCI except ESB, which was relatively lower. For cancer of larynx, there was no significant difference in UTCI among the five-beam arrangement methods. For cancers of maxillary sinus and parotid gland, the two BAO methods showed marginally higher UTCI among all the five methods. CONCLUSION: Individual methods showed dosimetric advantages on certain aspects, and the UTCI of the BAO treatment plans are marginally greater in the case of maxillary sinus and parotid gland. However, if treatment time was included into consideration, VMAT plans would be recommended for cancers of the nasopharynx, oral cavity, and larynx.

Intrafractional motion management in external beam radiotherapy.

The recent advancements in radiotherapy technologies have made delivery of the highly conformal dose to the target volume possible. With the increasing popularity of delivering high dose per fraction in modern radiotherapy schemes such as in stereotactic body radiotherapy and stereotactic body ablative therapy, high degree of treatment precision is essential. In order to achieve this, we have to overcome the potential difficulties caused by patient instability due to immobilization problems; patient anxiety and random motion due to prolonged treatment time; tumor deformation and baseline shift during a treatment course. This is even challenging for patients receiving radiotherapy in the chest and abdominal regions because it is affected by the patient's respiration which inevitably leads to tumor motion. Therefore, monitoring of intrafractional motion has become increasingly important in modern radiotherapy. Major intrafractional motion management strategies including integration of respiratory motion in treatment planning; breath-hold technique; forced shallow breathing with abdominal compression; respiratory gating and dynamic real-time tumor tracking have been developed. Successful intrafractional motion management is able to reduce the planning target margin and ensures planned dose delivery to the target and organs at risk. Meanwhile, the emergency of MRI-linear accelerator has facilitated radiation-free real-time monitoring of soft tissue during treatment and could be the future modality in motion management. This review article summarizes the various approaches that deal with intrafractional target, organs or patient motion with discussion of their advantages and limitations. In addition, the potential future advancements including MRI-based tumor tracking are also discussed.

Dynamics of oxygen level-driven regulators in modulating autophagy in colorectal cancer cells.

Colorectal cancer is a common cancer with metachronous distant metastases still threatening overall survival. Tumor oxygen level influences tumor radiosensitivity in relation to autophagy and apoptosis. The objective of this study is to evaluate the expression and interaction between multiple key regulators in different oxygen levels. Human colorectal adenocarcinoma HT-29 cells were cultured in 1% or 10% oxygen level and irradiated by 2 Gy with different incubation time. Autophagy key regulators, AMPK, HIFs and JNK were evaluated by Western blot. Sequential autophagy key regulator activation was observed in the order of AMPK, HIF-1α, HIF-2α and JNK. 10% oxygen level could promote autophagy with similar degree of autophagy activation as 1% oxygen level in 48-h while irradiation could slightly inhibit autophagy. The results of this study supported prior evaluation of oxygen level and autophagy regulators for improving treatment efficacy and indicated the possible directions in developing individualized radiotherapy by selective targeting of hypoxic regions.

A Review on the Special Radiotherapy Techniques of Colorectal Cancer.

Colorectal cancer is one of the commonest cancers worldwide. Radiotherapy has been established as an indispensable component of treatment. Although conventional radiotherapy provides good local control, radiotherapy treatment side-effects, local recurrence and distant metastasis remain to be the concerns. With the recent technological advancements, various special radiotherapy treatment options have been offered. This review article discusses the recently-developed special radiotherapy treatment modalities for various conditions of colorectal cancer ranging from early stage, locally advanced stage, recurrent, and metastatic diseases. The discussion focuses on the areas of feasibility, local control, and survival benefits of the treatment modalities. This review also provides accounts of the future direction in radiotherapy of colorectal cancer with emphasis on the coming era of personalized radiotherapy.

Development of a normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism in nasopharyngeal carcinoma patients.

BACKGROUND: The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. METHODS: Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy. Logistic regression with leave-one-out cross-validation was performed to establish the NTCP model. Model performance was evaluated and compared by the area under the receiver operating characteristic curve (AUC) in our NPC cohort. RESULTS: With a median follow-up of 24 months, 39 (22.4%) patients developed biochemical hypothyroidism. Gender, chemotherapy, the percentage thyroid volume receiving more than 50 Gy (V50), and the maximum dose of the pituitary (Pmax) were identified as the most predictive factors for RHT. A NTCP model based on these four parameters were developed. The model comparison was made in our NPC cohort and our NTCP model performed better in RHT prediction than the other four models. CONCLUSIONS: This study developed a four-variable NTCP model for biochemical hypothyroidism in NPC patients post-radiotherapy. Our NTCP model for RHT presents a high prediction capability. TRIAL REGISTRATION: This is a retrospective study without registration.

A longitudinal evaluation of early anatomical changes of parotid gland in intensity modulated radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space involvement.

INTRODUCTION: Radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space (PPS) involvement may deliver high dose to the parotid gland. This study evaluated parotid gland changes during and up to 3 months after radiotherapy. METHODS: Kilovoltage computed tomography (CT) scans of head and neck region of 39 nasopharyngeal carcinoma patients with PPS involvement were performed at pre-radiotherapy, 10th, 20th and 30th fractions and 3 months after treatment. The parotid glands were contoured in pre-radiotherapy planning CT scan and in subsequent scans. Dice similarity coefficient (DSC), percentage volume change and centroid movement between the planning CT and the subsequent CTs were obtained from the contouring software. In addition, the distance between medial and lateral borders of parotid glands from the mid-line at various time intervals were also measured. RESULTS: The ipsilateral parotid gland received a mean dose of about 5 Gy higher than the contralateral side. The mean DSC and parotid volume decreased by more than 30% at 20th fraction and reached the minimum at 30th fraction. Partial recovery was observed at 3 months after treatment. The centroid displacement followed a similar pattern, which moved medially and superiorly by an average of 0.30 cm and 0.18 cm, respectively, at 30th fraction. The changes in ipsilateral gland were slightly greater than the contralateral side. CONCLUSIONS: Substantial volume change and medial movement of parotid gland were observed with slightly greater magnitude in the ipsilateral side. Adaptive radiotherapy was suggested at around 15th to 20th fraction so as to optimise the original dose distribution of the plan.

Comparison of set up accuracy among three common immobilisation systems for intensity modulated radiotherapy of nasopharyngeal carcinoma patients.

INTRODUCTION: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, an effective immobilisation system is important to minimise set up deviation. This study evaluated the effectiveness of three immobilisation systems by assessing their set up deviations. METHODS: Patients were randomly assigned to one of the three immobilisation systems: (1) supine on head rest and base plate (HB); (2) supine with alpha cradle supporting the head and shoulder (AC); (3) supine with vacuum bag supporting the head and shoulder (VB). CBCT was conducted weekly for each patient on the linear accelerator. Image registration was conducted at the nasopharynx (NP) and cervical regions. The translational displacements (latero-medial, antero-posterior and cranio-caudal), rotational displacements (pitch, yaw and roll) and 3D vectors obtained at the NP and cervical regions were recorded and compared among the three systems. RESULTS: The mean translational and rotational deviations were within 3 mm and 2°, respectively, and the range of 3D vector was 1.53-3.47 mm. At the NP region, the AC system demonstrated the smallest translational and rotational deviations and 3D vector. The differences were significant except for the latero-medial, yaw and roll directions. Similarly, at the cervical region, the AC system showed smaller translational and rotational deviations and 3D vector, with only the cranio-caudal and yaw deviations that did not reach statistical significance. CONCLUSIONS: Set up deviation was greater in the neck than the NP region. The set up accuracy of the AC system was better than the other two systems, and it is recommended for IMRT of NPC patients in our institution.

The impact of positron emission tomography on primary tumour delineation and dosimetric outcome in intensity modulated radiotherapy of early T-stage nasopharyngeal carcinoma.

BACKGROUND: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC), accurate delineation of the gross tumour volume (GTV) is important. Image registration of CT and MRI has been routinely used in treatment planning. With recent development of positron emission tomography (PET), the aims of this study were to evaluate the impact of PET on GTV delineation and dosimetric outcome in IMRT of early stage NPC patients. METHODS: Twenty NPC patients with T1 or T2 disease treated by IMRT were recruited. For each patient, 2 sets of NP GTVs were delineated separately, in which one set was performed using CT and MRI registration only (GTVCM), while the other set was carried out using PET, CT and MRI information (GTVCMP). A 9-field IMRT plan was computed based on the target volumes generated from CT and MRI (PTVCM). To assess the geometric difference between the GTVCM and GTVCMP, GTV volumes and DICE similarity coefficient (DSC), which measured the geometrical similarity between the two GTVs, were recorded. To evaluate the dosimetric impact, the Dmax, Dmin, Dmean and D95 of PTVs were obtained from their dose volume histograms generated by the treatment planning system. RESULTS: The overall mean volume of GTVCMP was greater than GTVCM by 4.4 %, in which GTVCMP was slightly greater in the T1 group but lower in the T2 group. The mean DSC of the whole group was 0.79 ± 0.05. Similar mean DSC values were also obtained from the T1 and T2 groups separately. The dosimetric parameters of PTVCM fulfilled the planning requirements. When applying this plan to the PTVCMP, the average Dmin (56.9 Gy) and D95 (68.6 Gy) of PTVCMP failed to meet the dose requirements and demonstrated significant differences from the PTVCM (p = 0.001 and 0.016 respectively), whereas the doses to GTVCMP did not show significant difference with the GTVCM. CONCLUSION: In IMRT of early stage NPC, PET was an important imaging modality in radiotherapy planning so as to avoid underdosing the PTV, although its effect on GTV delineation was not significant. It was recommended that PET images should be included in the treatment planning of NPC patients.

Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.

A split-parotid delineation approach for dose optimization in volumetric modulated arc therapy for nasopharyngeal carcinoma patients with parapharyngeal space invasion and level IIa cervical lymph node involvements.

OBJECTIVE: This study evaluated the potential benefit of a split-parotid delineation approach on the parotid gland in the treatment planning of patients with nasopharyngeal carcinoma (NPC). METHODS: 50 patients with NPC with parapharyngeal space (PPS) and/or level IIa cervical node involvements were divided into three groups: PPS only, level IIa cervical node only and both. Two volumetric-modulated arc therapy plans were computed. The first plan (control) was generated based on the routine treatment-planning protocol, while the second plan (test) was computed with the split-parotid delineation approach, in which a line through the anterolateral margin of the retromandibular vein was created that divided the parotid gland into anterolateral and posteromedial subsegments. For the test plan, the anterolateral subsegment was prescribed, with a dose constraint of 25 Gy in the plan optimization. Dosimetric data of the parotid gland, target volumes and selected organs at risk (OARs) were compared between the control and test plans. RESULTS: The mean dose to the anterolateral subsegment of the parotid gland in all three groups was kept below 25 Gy. The test plan demonstrated significantly lower mean parotid dose than the control plan in the entire gland and the anterolateral subsegment in all three groups. The difference was the greatest in Group 3. CONCLUSION: The split-parotid delineation approach significantly lowered the mean dose to the anterolateral subsegment and overall gland without greatly compromising the doses to target volumes and other OARs. The effect was more obvious for both PPS and level IIa cervical node involvements than for either of them alone. ADVANCES IN KNOWLEDGE: It is the first article based on the assumption that parotid gland stem cells are situated at the anterolateral segment of the gland, and applied the split-parotid delineation approach to the parotid gland in the treatment planning of patients with NPC with PPS and level IIa cervical node involvements, so that the function of the post-radiotherapy parotid gland might be better preserved.

Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis. However, neck RT may induce the development of carotid atherosclerosis. The mechanisms of radiation-induced carotid atherosclerosis are still unclear and no previous study has investigated the genetic involvement of radiation-induced carotid atherosclerosis. The present study aims to determine the association between genetic polymorphisms and carotid atherosclerosis in patients treated with RT for nasopharyngeal carcinoma. METHODS: The present study recruited 128 post-RT NPC patients. Carotid plaque score was assessed using ultrasonography. Thirteen single nucleotide polymorphisms (SNPs) that affect the function of anti-atherosclerotic genes, including SOD2, SOD3, CAT, PON1, PPARG, ADIPOQ, IL10, TGFB1 and NOS3, were genotyped. Association between the 13 SNPs and carotid atherosclerosis was evaluated using multiple regression after adjustment for covariates (PLINK). Multiple testing was corrected using Benjamini-Hochberg step-up false discovery rate controlling procedure. RESULTS: rs662 and rs705379 of PON1 were close to be significantly associated with carotid plaque score (Corrected P value, P cor =0.0528 and P cor =0.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (P cor < 0.05). None of the other SNPs showed significant association with carotid plaque score. CONCLUSIONS: TC haplotype in rs662-rs705379 of PON1 is likely to be a genetic risk factor of carotid plaque score. Post-RT NPC patients with the TC haplotype may need earlier and more frequent carotid ultrasound examinations for early detection of carotid atherosclerosis.

Sonographic appearance of thyroid glands in patients treated with intensity-modulated radiotherapy or conventional radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to investigate the sonographic appearances of the thyroid glands in nasopharyngeal carcinoma (NPC) patients whose cervical lymph nodes were treated with conventional radiotherapy (RT) or intensity-modulated radiotherapy (IMRT). The post-RT sonographic appearances of the thyroid glands in NPC patients were also correlated with the thyroid function. METHODS: One hundred and three NPC patients who had completed RT of cervical lymph nodes using the anterior cervical field, 30 NPC patients who had completed RT of cervical lymph nodes using IMRT, and 61 healthy subjects were included in the study. Thyroid glands were sonographically assessed for their size, echogenicity, vascularity, and internal architecture. Thyroid function tests were also performed on each subject. RESULTS: In comparison with the patients with abnormal thyroid function, the thyroid glands of the patients with normal thyroid function tended to be homogeneous and to have greater volume and echogenicity index (p < 0.05). Compared with those of the healthy subjects, the thyroid glands of patients previously treated with IMRT and those treated with the anterior cervical field showed significantly lower thyroid volume, lower incidence and number of nodules, and higher vascularity index (p < 0.05). CONCLUSIONS: The patient's history of previous RT should be taken into consideration in the sonographic examination of the thyroid gland post-RT. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:210-223, 2015.