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Supplementary Table 1 from Gα12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization

Supplementary Figures 1-3 from Gα12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization

Supplementary Table 2 from Gα12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization

Supplementary Table 3 from Gα12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization

Background The purpose of this study is to analyze the impact of post-operative radiotherapy on the results in patients with intracranial hemangiopericytoma (HPC). Materials and methods We retrospectively reviewed 66 intracranial HPC patients between 1999 and 2019 including 29 with surgery followed by radiotherapy (11 with intensity-modulated radiotherapy (IMRT) and 18 with stereotactic radiosurgery (SRS)) and 37 with surgery alone. Chi-squared test was used to compare the clinical characteristic between the groups. The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox proportional hazards models were used to examine prognostic factors of survival. Results The crude local control rates were 58.6% in the surgery plus post-operative radiotherapy group (PORT) and 67.6% in the surgery alone group (p = 0.453). In the subgroup analysis of the PORT patients, local controls were 72.7% in the IMRT group and 50% in the SRS group (p = 0.228). The median OS in the PORT and surgery groups were 122 months and 98 months, respectively (p = 0.169). The median RFS was 96 months in the PORT group and 72 months in the surgery alone group (p = 0.714). The median OS and RFS of the SRS group were not significantly better than those in the IMRT group (p = 0.256, 0.960). The median RFS were 112 and 72 months for pathology grade II and III patients, respectively (p = 0.001). Conclusion PORT did not improve the local control rates nor the survivals. The local control rates after IMRT and SRS were similar even though the IMRT technique had a much higher biological dose compared with the SRS technique. PORT is not indicated for intracranial HPC patients with a complete resection margin.

BACKGROUND The purpose of this study was to present our comparison of the clinical outcome of patients with nasopharyngeal carcinoma (NPC) treated with whole-field intensity-modulated radiotherapy (whole-field-IMRT) or split-field-IMRT. METHODS We retrospectively studied 388 patients with M0 NPC. The median lower neck doses were 50 Gy in 1.35 Gy/fractions for the 240 whole-field-IMRT patients, and 50.4 Gy in 1.8 to 2.0 Gy/fractions for the 148 split-field-IMRT patients. RESULTS The IMRT technique did not affect the overall survival (OS; P = .077) and locoregional control (P = .231) rates. However, the split-field-IMRT group had more locoregional recurrences at the whole neck (P = .005) but not at the nasopharynx (P = .968) or the lower neck (P = .485). The patients treated with split-field-IMRT (43.2%) had more grade III neck fibrosis than the patients who received whole-field-IMRT (18.3%; P < .001). Only 1 patient had temporal lobe necrosis in our study. CONCLUSION Our study shows that whole-field-IMRT using a lower dose/fraction for the lower neck results in at least comparable locoregional control and less fibrosis compared to conventional fraction with split-field-IMRT.

BACKGROUND The purpose of this study was to assess the predictive factors of optic neuropathy among patients with nasopharyngeal carcinoma (NPC). METHODS The analysis included 16 297 patients with NPC and 65 187 controls. Each patient with NPC was randomly frequency-matched with 4 individuals without NPC by age, sex, and index year. Cox proportional hazard models were applied to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) of optic neuropathy development associated with NPC. RESULTS The risk of optic neuropathy was significantly higher in the NPC cohort (adjusted HR [aHR] 3.42; 95% CI 2.85-4.09; P < .001). Independent risk factors for optic neuropathy among patients with NPC included stroke (aHR 1.7; 95% CI 1.07-2.7; P = .03) and receipt of chemotherapy (aHR 1.55; 95% CI 1.17-2.06; P = .002). CONCLUSION The risk of optic neuropathy was significantly higher in patients with NPC than in the general population.

To investigate if dose escalation using intracavitary brachytherapy (ICBT) improves local control for nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT) and concurrent chemoradiation treatment (CCRT). We retrospectively analyzed 232 patients with Stage T1–3 N0–3 M0 NPC who underwent definitive IMRT with or without additional ICBT boost between 2002 and 2013. For most of the 124 patients who had ICBT boost, the additional brachytherapy was given as 6 Gy in 2 fractions completed within 1 week after IMRT of 70 Gy. CCRT with or without adjuvant chemotherapy was used for 176 patients, including 88 with and 88 without ICBT boost, respectively. The mean follow-up time was 63.1 months. The 5-year overall survival and local control rates were 81.5% and 91.5%, respectively. ICBT was not associated with local control prediction (P = 0.228). However, in a subgroup analysis, 75 T1 patients with ICBT boost had significantly better local control than the other 71 T1 patients without ICBT boost (98.1% vs 85.9%, P = 0.020), despite having fewer patients who had undergone chemotherapy (60.0% vs 76.1%, P = 0.038). Multivariate analysis showed that both ICBT (P = 0.029) and chemotherapy (P = 0.047) influenced local control for T1 patients. Our study demonstrated that dose escalation with ICBT can improve local control of the primary tumor for NPC patients with T1 disease treated with IMRT, even without chemotherapy.

We investigated to what extent can the dose-volumes of the coronary artery and the cardiac substructures be reduced by using IMRT technique in left-sided breast cancer patients. We chose 40 pN2M0 patients treated with postmastectomy IMRT. The original treatment plans were retrieved and the (internal mammary nodes) IMNs and cardiac substructure delineations were added. Three sets of dose-volume parameters including the original plans without internal mammary irradiation (IMNI), the plans with IMNI, and the plans with dose constraints to the heart, were derived. In left-sided patients, when IMNI was included, the V30 for right ventricle (RV), left ventricle (LV), pulmonic valve (PV), and left anterior descending artery (LADA) were 56.37% ± 7.9%, 25.3% ± 7.3%, 48.3% ± 6.3%, and 69.7% ± 6.4%, respectively. Of the 4 main coronary arteries, LADA had the highest dose followed by the left main coronary artery (LMCA). LADA had a V40 of 62% ± 9.7% vs 13.5% ± 3.5%, and a V50 of 27.5% ± 4.7% vs 0, with and without IMNI. For the right-sided patients, the V30s for all the heart substructures were 0 with or without IMNI. When we set a dose constraint of V4010% for the LADA in the left-sided patients, the PTV volumes covered by 50 Gy decreased by only 1%. IMNI increased the V30 of the right and left ventricle and significantly increased the V40 and V50 to the LADA of left-sided breast cancer patients. IMRT markedly reduces the dose to the main coronary arteries and the right and left ventricle.

Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this “phantom tumor” phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis. In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed. Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38–121 months without anti-cancer treatments. Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the “phantom tumor phenomenon”, is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.

This study presents a technique requiring relatively simple supporting devices and protection accessories for treating conditions like mycosis fungoides in which a uniform radiation dose to the whole body can be achieved by using the regular largest electron cone instead of HDRe[Formula: see text] mode in one treatment course. The regular cone total skin electron therapy technique presented in this study is able to deliver a uniform radiation dose to the patient’s skin surface. The result is satisfying when compared with the High Dose Rate e[Formula: see text] (HDRe[Formula: see text]) Stanford Six Field Technique.

Purpose. We developed a mathematic empirical model for describing the small field penumbra in order to analyze the potential dose perturbation caused by overlapping field to avoid the dose calculation errors in linear accelerator-based radiosurgery. Materials and methods. A ball phantom was fabricated for measuring penumbra at 4 different gantry angles in the coplanar plane. A least square root estimation (LSRE) Model was created to fit the measured penumbra dose profile and to predict the penumbra dose profile at any gantry angles. The Sum of Squared Errors (SSE) was used for finding the parameters n and t for the best fitting of the LSRE model. Geometric and mathematical methods were used to derive the model parameters. Results. The results showed that the larger the gantry angle of the field, the more the expansion of the penumbra dose profile. The least square root estimation model for describing small field penumbra is as follows: PenumbraDš=T⋅1/2⋅1−š/n+š2+t where PenumbraDš denotes the dose profile D(š) at the penumbra region, T is the penumbra height (usually in scalar 100), n is the parameter for curvature, š = x − Wd/2 (x and š are the values in cm on x-axis), and t is the radiation transmission of the collimator. Geometric analysis establishes the correlation between the penetration depth of the exposure and its effect on the penumbra region in ball phantom. The penumbra caused by an exposure at any arbitrary angles can be geometrically derived by using a one-variable quadratic equation. Conclusion. The dose distribution in penumbra region of small field can be created by the LSRE model and the potential overdosage or underdosage owing to overlapping field perturbation can be estimated.

The construction of a conventional prostate needle (seeds) implant template restricts needles tilting or incline insertion when it is necessary to approach a seminal vesicle or to avoid the obstruction of symphysis pubis. To overcome the disadvantages of conventional templates, we developed a special template for guiding needles incline insertion and fixation for prostate needle implant. Phantom needles implantation was performed. Two acrylic boards, each 7.5 cm in width by 7.5 cm in length and 0.5 cm thickness, were drilled with a set of domed holes and cones with embedded template ball inside this combination to provide firm grip and fixation in prostate needle implantation. The specially designed domed‐cones combination acrylic board provides a needle of up to 60° rotation flexibility application. Some areas that could not be covered in a conventional parallel needle holes template could now be covered by using this new template. The covering index of prostate radiation dosage is up to 84.5%. The specially designed domed‐cones acrylic board combination provides not only a reliable means of needle fixation and rotational function, but also a superior dose distribution in the anterior portion of the prostate and good coverage of a seminal vesicle. This special template is a feasible design for prostate needles or seeds implant brachytherapy. PACS number(s): 87.57.uq

Objectives Survival in patients with locally advanced unresectable pancreatic cancer (LAUPC) is poor, and local recurrence continues to be a major problem in the management of this disease. Radiotherapy (RT) using different RT techniques, including intensity-modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT), may lead to different clinical outcomes for patients with LAUPC. Here, we compared SBRT with IMRT for patients with LAUPC with respect to survival rate, local control (LC) rate, and toxicity-related dose distribution. Materials and methods This retrospective study from March 2007 to March 2011 included 41 patients with LAUPC who were divided into two groups, with 20 patients receiving SBRT and 21 patients receiving IMRT. The median follow-up time was 16 months. Results For the IMRT and SBRT groups, the median survival times were 13 and 20 months, and 1-year overall survival (OS) rates were 70.7 and 80.0%, respectively. There was no difference in OS between the two RT techniques. RT with SBRT showed significantly better local disease-free survival than IMRT for patients with LAUPC. Tobacco use had a borderline effect on LC. Thus, further statistical analysis showed that patients who used tobacco had better LC after receiving SBRT than IMRT. Conclusion SBRT improved LC for LAUPC patients and had similar radiation toxicity compared with IMRT. Further study is required to define the effects of administered radiation dose and fractionation, as well as to further expand the sample size, to use a prospective study, and to observe the long-term efficacy of these techniques.

Background and Aim This study aimed to evaluate the outcomes and toxicities of repeated stereotactic ablative radiotherapy (SABR) in hepatocellular carcinoma (HCC). Methods Fourteen HCC patients with local recurrence (18 lesions) after liver SABR received repeated radiotherapy with SABR using CyberKnife. No patients experienced radiation-induced liver disease after the first SABR course. The median first SABR dose was 41 Gy (range, 34–60 Gy); the median second SABR dose, 40 Gy (range, 25–50 Gy); and the median interval, 12.9 months. Local recurrence was divided into in-field recurrence and out-field recurrence. Results Objective responses were observed in 11 tumors (61.1%), including five tumors (27.8%) with complete responses. Intrahepatic out-field failure was the main cause of treatment failure (7 of 14 patients). In-field failure had developed in 1 of 18 tumors (5.6%), resulting in a 2-year in-field failure-free rate of 88.2%. The median time to progression was 14.0 months, with 1- and 2-year progression-free survival rates of 68.6% and 42.9%, respectively. One- and two-year overall survival rates were 76% and 59.1%, respectively. Of the 14 patients, one developed radiation-induced liver disease and three showed progression of the Child-Turcotte-Pugh class after the second SABR course. Other toxicities were generally mild and tolerable. Conclusion Repeated SABR in selected HCC patients is feasible with acceptable toxicity.

The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife® stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12–40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife® was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated.

Background The purpose of this study was to examine the risk of nasopharyngeal carcinoma (NPC) after a diagnosis of allergic rhinitis. Methods We identified 67,532 patients with allergic rhinitis (allergic rhinitis cohort) and a 135,064 control cohort with the same mean age and sex ratio by using a Taiwan Longitudinal Health Insurance Database (LHID) sample from 2000 to 2005. Results After adjusting for the possible confounding factors of the study, the allergic rhinitis cohort had a 2.33-fold higher risk of developing NPC than did the comparison cohort. The frequency of allergic rhinitis visits was correlated with the risk of subsequent NPC. Patients with 4 or more allergic rhinitis visits per year were significantly associated with increasingly developing NPC risk. Conclusion Patients with allergic rhinitis might be associated with subsequent NPC in Taiwan. Those who had repeated visits for allergic rhinitis had even higher risk for NPC. Physicians should be aware of the link when assessing patients with allergic rhinitis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 413–417, 2015

The role of stereotactic ablative radiotherapy (SABR) in patients with hepatocellular carcinoma (HCC) who are refractory to or unsuitable for transarterial chemoembolization remains unclear. We examined the efficacy and safety of Cyberknife SABR and its effect on survival in this group of HCC patients.From June 2008 to June 2011, 53 patients with 68 tumors of unresectable HCC were treated using Cyberknife SABR. The tumors measured 1.1-13 cm (median, 4.3 cm). The median prescribed dose was 40 Gy in four to five fractions over 4-5 consecutive working days.The median follow-up period was 13.1 months for all patients and 18.1 months for the living patients. Objective responses were observed in 48 of 67 tumors (71.6%), including 22 tumors (32.8%) with complete responses. The 1- and 2-year in-field failure-free rate was 73.3 and 66.8%, respectively. Out-field intrahepatic recurrence was the main cause of treatment failure (28/52 patients). The median survival time was 20.0 months, and the 1- and 2-year overall survival rate was 70.1 and 45.4%, respectively. Multivariable analysis showed that Eastern Cooperative Oncology Group performance status (≤1 vs.1) and tumor response (responder vs. nonresponder) were independent prognostic factors for overall survival. Radiation-induced liver disease, including classic and nonclassic types, developed in five patients (9.4%). Other acute toxicities were generally mild and tolerable.Our findings supported the feasibility of SABR as a salvage treatment for HCC when transarterial chemoembolization was ineffective or technically unsuitable. Additional efforts to improve the response rate and reduce out-field recurrence are required.

We report a case of infantile fibrosarcoma in an 8-month-old boy manifested as a right-sided lower leg mass. Repeated local recurrence and distant metastasis were noted during the following three-year period. Whole body fluoro-deoxyglucose positron emission tomography scan revealed an asymptomatic metastasis involving the fourth lumbar vertebrae. The patient received chemotherapy (VAC regimen) with Cyberknife® stereotactic hypofractionated radiotherapy (26 Gy; 4 fractions). This treatment reduced tumor size by 23% without acute radiation toxicity even after 33 months. This case suggests that combining chemotherapy and this form of radiotherapy may be safe and effective against childhood spinal metastasis.

The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted.

Purpose To investigate parotid perfusion in early-to-intermediate stage after parotid-sparing radiation dose using fat-saturated DCE-MRI, and to verify whether the perfusion alteration was related to radiation dose and the PSV. Methods and Materials Thirty-two parotid glands from 16 consecutive patients with pathologically proven nasopharyngeal carcinoma treated by IMRT were examined. The parotid glands received a radiation dose of 28.9 ± 3.9 Gy with a PSV of 43.1% ± 13.9%. Perfusion parameters were calculated using time-shifted Brix model from fat-saturated DCE-MRI data before (pre-RT) and in early-to-intermediate stage after (post-RT) IMRT. Paired t-test was used to evaluate perfusion changes, while Pearson's correlation test was used to examine perfusion dependency on radiation dose and PSV. For multiple comparisons Bonferroni correction was applied. Results Successful fat saturation was achieved in 29 of 32 parotid glands. Compared with pre-RT, the post-RT parotid glands showed significantly higher A, peak enhancement, and wash-in slope, plus a lower Kel, suggesting a mixed effect of increased vascular permeability and acinar loss. Linear regression showed that peak enhancement was positively associated with radiation dose in post-RT parotid glands. Kel and slope were negatively associated with PSV, while time-to-peak was positively associated with PSV significantly. Conclusions Our results suggest that time-shifted Brix model is feasible for quantifying parotid perfusion using DCE-MRI. The perfusion alterations in early-to-intermediate stage after IMRT might be related to a mixed effect of increased vascular permeability and acinar loss with dose and PSV dependencies.

OBJECTIVE:To evaluate the survival outcomes and prognostic factors of patients with advanced hepatocellular carcinoma (HCC) who underwent stereotactic ablative radiotherapy (SABR). METHODS:This retrospective study evaluated patients with advanced HCC who underwent SABR between December 2007 and July 2015. All patients had Barcelona Clinic Liver Cancer stage C disease and Child-Turcotte-Pugh (CTP) class A-B function. In-field control (IFC), overall survival (OS), prognostic factors, and toxicity were evaluated. RESULTS:In this study of 89 patients, the 3-year IFC rate was 78.1%, and the 1-year and 3-year OS rates were 45.9% and 24.3%, respectively. The multivariate analysis revealed that CTP class, the presence of main portal vein tumor thrombosis, and the presence of extrahepatic spread were independent predictors of OS. The expected median OS values among patients with ≥2, 1, and 0 predictors were 4.2, 8.6, and 26.4 months, respectively (p

To evaluate the prognostic performance of the Child-Turcotte-Pugh (CTP) score and the albumin-bilirubin (ALBI) score in hepatocellular carcinoma (HCC) patients treated using stereotactic ablative radiation therapy (SABR).This retrospective study evaluated the data of patients with HCC who underwent SABR between December 2007 and June 2015. We collected pretreatment CTP and ALBI scores and analyzed their correlation with survival and liver toxicity.This study included 152 HCC patients: 78.3% of CTP class A and 21.7% of CTP class B. The median ALBI score was -2.49 (range, -3.67 to -0.84) with 39.5% of grade 1, 56.6% of grade 2, and 3.9% of grade 3. The CTP classification and ALBI grade were significantly associated with overall survival (P.001). Albumin-bilirubin grade (1 vs 2) had a trend to stratify CTP class A patients into 2 risk groups of mortality (P=.061). Combined CTP class and ALBI score could predict development of radiation-induced liver disease (2.4% in CTP A-ALBI -2.76, 15.1% in CTP A-ALBI ≥ -2.76, and 25.8% in CTP B).Albumin-bilirubin score is a potential predictor for both survival and liver toxicity. Complementary use of CTP and ALBI score could predict the risk of post-SABR liver toxicity. Further prospective studies are necessary before use of the ALBI score can become part of daily practice.

The purpose of this study was to realize the processing of dose distribution of RGK at the treatment isocenter at any gantry rotational angle by using an analytic geometry method to avoid inadequate arc therapy angles when implementing the treatment plan. Gaf chromic film was used for dose evaluation. A calibration curve was first obtained using linear accelerator irradiation. The 50% dose relative to the central axis at fixed gantry angles at the x-, y- and z-axes was obtained using Gaf chromic film and was compared to the analytic geometry method. The full width half maximum (FWHM) on the x-, y- and z-axes was predicted for the RGK dose distribution characteristic analysis. The FWHM on the x-, y-, and z-axes varies with different gantry and rotational plate angles. The most dramatic intersection variation appeared at a static gantry angle of 25°. The ratio of the FWHM of the y- and z-axes to that of the x-axis was up to 9 and 10. The geometric analytic method can be used for an accurate analysis of dose distribution in RGK replacing the actual film exposure experiment. It is essential to select the best arc irradiation angle to prescribe the dose to avoid excess irradiation of normal tissue. The geometric method used in this study can also be applied for rotational arc therapy dose analysis such as tomotherapy, linear-based stereotactic radiotherapy, or volume matrices arc therapy.

Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic. In this report, we presented the case of an 82-year-old patient with poorly differentiated lung adenocarcinoma and asymptomatic eosinophilia. The patient's condition worsened rapidly over a week, with episodes of cognitive disturbance, shortness of breath and acute kidney dysfunction. These symptoms were associated with a 4-fold increase in circulating eosinophil counts. The poor condition hindered further anticancer treatment. Treatment of the eosinophilia with corticosteroids and hydroxyurea significantly reduced circulating eosinophil counts to below the initial levels. Results of this case report suggested that lung cancer patients should be monitored closely for rapidly worsening symptoms of cognitive disturbance and respiratory insufficiency as signs of life-threatening asymptomatic eosinophilia, in order to initiate corticosteroid treatment.

Purpose To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). Methods and Materials This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4–5 fractions over 4–5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. Results The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. Conclusion SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.

To determine whether the diagnosis of otitis media (OM) in adults is associated with an increased risk for the subsequent development of nasopharyngeal cancer (NPC) using a nationwide population-based retrospective study.We selected 13,513 adult patients that had been previously diagnosed with OM between 2000 and 2005 from the Taiwan Longitudinal Health Insurance Database 2000 as the study cohort, and randomly extracted the data of 135,130 participants matched by sex, age, and baseline year for the comparison cohort. The follow-up period was terminated upon developing NPC, withdrawal from the national health insurance system, or the end of 2009. Cumulative incidences and hazard ratios (HRs) of NPC development were determined.The subsequent NPC incidence rates in the OM and comparison cohorts were 6.41 and 0.58 per 10000 person-years, respectively (adjusted HR, 11.04; 95% CI, 7.68-5.87; P0.0001). The NPC risk for males was significantly higher than that for females (adjusted HR=3.24; 95% CI, 2.16-4.85). In both female and male patients, the diagnosis of OM was associated with a significantly increased risk for NPC (adjusted HR, 11.91 vs. 10.78, respectively). Among the OM cohort, 62 participants were subsequently diagnosed with NPC, with 71% of them occurring within 1 year following the diagnosis of OM. However, even after 5-year follow-up, the OM cohort still displayed a higher risk for NPC (adjusted HR=2.50). Stratified by the frequency of OM episodes, more than one episode per year had a significantly greater risk of developing NPC, compared with the comparison cohort (HR=29.22; 95% CI, 20.19-42.27).We found that adult OM is a warning sign for the development of NPC in Taiwan, with approximately an 11-fold higher risk for adult OM patients. We recommend that OM patients undergo follow-up examinations for at least 5 years. To extrapolate our findings, further studies are warranted in other areas in which NPC is endemic.

Background. The treatment results of buccal squamous cell carcinoma before and after 2002 were compared. Methods. Two hundred forty-five patients with buccal cancer who underwent curative treatment were retrospectively reviewed. Results. The 5-year overall survival rate was 30.0% before 2002 and 53.5% after 2002 (p ¼ .004). On multivariate analysis, T classification, surgical margins, and treatment modality significantly affected overall survival, and N classification and histologic grade had trends to affect it. Invasion depth had a trend to influence locoregional control. For patients with early- stage disease without adverse factors, the locoregional control was similar between surgery alone group and surgery þ radiotherapy group. Conclusion. The survival of patients with buccal cancer was improved after 2002, which represented the start of intensity-modulated radiotherapy (IMRT) in our institute. Ipsilateral neck alone irradiation was recommended for T1-2N0-1 and small T3N0 disease, and bilateral neck irradiation could be reserved for advanced disease. V C 2012 Wiley Periodicals, Inc. Head Neck 35: 65-71, 2013

Purpose To test, in a retrospective matched-pair study, whether necrosis-rescuing hyperbaric oxygen therapy (HBOT) increases the risk of cancer re-recurrence in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. Methods and materials Between January 1995 and July 2004, we retrospectively identified 22 patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. We defined two groups: the HBOT group, 11 patients with HBOT for rescuing late radiation-associated tissue necroses; and the non-HBOT group, the other 11 matched-pair patients without HBOT. Between the two groups, the following four factors were matched for case pairing: primary cancer subsite, initial cancer stage, age, and gender. Results Three findings indicate that HBOT increases the risk of cancer re-recurrence. First, we observed more cancer re-recurrences in the HBOT group than in the non-HBOT group: 9 of 11 vs. 4 of 11, with 5-year disease-free survival rates after salvage of 32.7% vs. 70.0% (hazard ratio 3.2; 95% confidence interval 1.03–10.7; p = 0.048). Second, re-recurrences developed rapidly after HBOT in 6 patients. Third, 3 patients had unusual cancer re-recurrences after HBOT. Remarkably, of 9 patients with cancer re-recurrences in the HBOT group, 4 patients had cancer disease-free intervals of 9 months or less before HBOT. Conclusions Necrosis-rescuing HBOT should be given with caution in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers; if it cannot be omitted entirely, deferring HBOT 9 months or longer after cancer re-treatment may be prudent.

The purposes of this study were to (a) explore the impact of xerostomia and saliva flow on quality of life and (b) validate the Taiwanese version of the Xerostomia Questionnaire (XQ) for patients undergoing radiotherapy (RT) for head and neck cancer in Taiwan. This was a prospective longitudinal study. Instruments consisted of the Xerostomia Questionnaire-Taiwan version (XQ-T) and the Medical Outcomes Study Short Form-36 Taiwan Version. Salivary output was measured by collecting unstimulated whole saliva. The questionnaires and measurements of salivary output were completed before RT was initiated and at two, four, six, and eight weeks after RT had started. Changes in xerostomia scores, quality of life, saliva flow, and predictors of quality of life over time were examined by using general estimating equations. The XQ-T is the first xerostomia measurement instrument developed for use with Taiwanese cancer patients and demonstrated excellent reliability and validity. Saliva flow was significantly correlated with XQ-T scores at two, four, six, and eight weeks after RT had started, but not before RT had begun. Saliva flow and quality-of-life scores significantly diminished and xerostomia scores significantly increased over the eight-week period. Saliva flow and XQ-T scores significantly predicted quality of life, after adjusting for the maturation effect. The results of this study show that the XQ-T is the first xerostomia measurement instrument to be developed for Taiwanese cancer patients and demonstrates excellent reliability and validity.

Primary malignant fibrous histiocytoma of thyroid is extremely rare. Only three cases have been reported. We report two cases of this rare disease. Case 1 was a 70-year-old woman who had Graves' disease and a growing 3.5-cm thyroid nodule with constrictive symptoms. Fine-needle aspiration cytology showed suspicious atypical cells. She had a total thyroidectomy; frozen section showed sarcoma. Final pathology showed malignant fibrous histiocytoma. Case 2 was a 67-year-old woman who had a 5-cm thyroid nodule that rapidly grew, causing tracheal deviation. A diagnostic lobectomy and pathology showed malignant fibrous histiocytoma. She then had a completion total thyroidectomy. Neither patient had metastatic lesions found by whole body gallium scans, computerized tomographic scans, and neck sonography. Both patients had postoperative radiotherapy and were alive and without recurrence at 6 months follow-up.

Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma. The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases—underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response. The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.

The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations. This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle3 with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume. In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques. IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted.

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

Background and purpose This study examined the efficacy of parotid gland sparing of three-dimensional conformal radiotherapy (3DCRT) compared with conventional radiotherapy for NPC patients. Both the dose given to the parotids and clinical assessment of dry mouth were conducted. Materials and methods Dry mouth was assessed for 108 patients treated with conventional technique and 72 treated with 3DCRT. Dose analysis was performed in 48 patients of the 3DCRT group. A dose of 70 Gy was given to the midplane in conventional radiotherapy and to 90% isodose volume in 3DCRT. Prognostic factors affecting the severity of dry mouth were analyzed using Generalized Estimating Equation (GEE). Results In the 3DCRT group about 50% of the patients' parotid glands received less than 25 Gy. Parallel analysis of dry mouth shows a significant decrease in the incidence of severe xerostomia after 3DCRT. The proportion of patients without dry mouth was also significantly higher in the 3DCRT group than the conventional group at 1–3 years after completion of radiotherapy. Although 3DCRT delivered a higher dose to the tumor, it spared the parotid gland significantly better than the conventional treatment. Late toxicities were mostly similar between the 2 groups while local control in T4 patients and survival were improved for 3DCRT. Conclusion Dosimetrically and clinically 3DCRT is better than conventional technique regarding parotid gland protection.

Purpose To evaluate the long-term results of salvage radiotherapy for patients of invasive cervical cancer after inadequate surgery. Methods and materials Between October 1975 and January 1994, 90 patients were treated with radiotherapy for invasive cervical carcinoma after simple hysterectomy. The inadequate surgery was performed for a variety of reasons. All patients had postoperative external beam irradiation or intravaginal brachytherapy, or both. The end points of this study were local control, survival, and treatment-related toxicity. Results The patients' age varied between 33 and 76 with a median of 53 years. The most common histopathology was squamous cell carcinoma, which accounted for 91% of the patients. The most frequent reason for inadvertent hysterectomy was understaged disease with preoperative diagnosis as carcinoma in situ for 51 patients (57%). Malignancy was not suspected before surgery in 28 patients (31%). After surgery, 72 patients (80%) were restaged as Ib, 12 patients (13.3%) as IIa, and 6 patients (6.7%) as IIb. Median follow-up time was 83 months. Seventy-three patients had follow-up times of 5 years or more. The overall 5-year and 10-year survival rates of 90 patients were 85.5% and 74.1%, respectively. Disease-specific 5-year and 10-year survival rates were 85.5% and 80.5%, respectively. All 16 patients with either locoregional or distant failure eventually died of disease. Fourteen patients (15.5%) had late morbidities. Radiation proctitis developed in 6 patients, intestinal obstruction in 4 patients, and hemorrhagic cystitis in 3. There was only 1 patient (1%) with terminal ileum stenosis and severe intestinal obstruction requiring surgical intervention. Conclusions Most cases of inadequately treated invasive cervical cancer were the result of suboptimal preoperative workups. Patients who had early tumors and no gross residual tumor after inadequate hysterectomy can have excellent prognoses when given postoperative radiotherapy. The severe long-term complication related to salvage radiotherapy is rare.

Objectives We reported the contemporary survival outcome of patients with nasopharyngeal carcinoma (NPC) and analysed the factors affecting survival. Design A retrospective cohort study. Setting A nationwide population-based study in Taiwan. Participants We identified 13 407 patients with newly diagnosed NPC from 2002 to 2010. Material and Methods The multivariate Cox proportional hazards model was performed to measure the mortality-association risk factor in patients with NPC after adjusting for NPC treatment and socio-demographic characteristics. Results The 1-, 2-, 5- and 8-year overall survival (OS) rates were 89.6%, 80.4%, 65.2% and 56.5%, respectively. The factors associated with mortality risk were sex (men versus women, HR = 1.45), age (>60 versus ≤ 40 years, HR = 3.61), geographic region of residence (eastern Taiwan versus northern Taiwan HR = 1.39), income ( 25 000, HR = 1.87) and treatment modality (chemotherapy alone versus radiotherapy alone, HR = 2.25). Conclusion The contemporary 5-year OS rate was 65.2% in Taiwan. Male patients, old age, residing in eastern Taiwan, low income and receiving chemotherapy alone were independent predictors for poor OS.