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Background: The aim of this study is to evaluate the outcomes and prognostic factors in patients with hepatocellular carcinoma (HCC) and Child–Turcotte–Pugh (CTP) class B liver function after stereotactic ablative radiotherapy (SABR). Materials and Methods: This retrospective study evaluated patients with HCC and impaired liver function who underwent SABR between December 2007 and August 2016. All patients had CTP class B liver function before treatment. Local control (LC) rate, overall survival (OS) rate, prognostic factors, and radiation-related toxicity were evaluated. Results: This study included 34 patients. The majority had a CTP score of B7 (52.9%) and advanced HCC (91.2%). The median survival time was 4.8 months, and the 1-year OS rate was 21.4%. Only the tumor number (multiple vs. single) was identified as an independent predictor of survival. The 1-year LC rate was 95.8%. Eight patients (23.5%) developed the radiation-induced liver disease, and 15 (44.1%) had a CTP score decline of ≥2 within 3 months. Other toxicities were generally tolerable. Conclusion: SABR may be considered as an alternative option for patients with HCC and CTP class B liver function, particularly for those with a single lesion.

Background Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value. Methods In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the β-value from CpG probes based on sequencing with the Illumina Human 450 K platform. Results A high mean DNAm (β > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value XBP1 expression level and higher proportion of hormone-positive BC (p value Conclusions Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

Background : Stereotactic body radiotherapy (SBRT) is an effective but less focused alternative for treatment of hepatocellular carcinoma (HCC). To date, a personalized model for predicting therapeutic response is lacking. This study aimed to review current knowledge and to propose a radiomics-based machine-learning (ML) strategy for local response (LR) prediction. Methods : We searched the literature for studies conducted between January 1993 and August 2019 that used > 100 patients. Additionally, 172 HCC patients in our hospital were retrospectively analyzed between January 2007 and December 2016. In the radiomic analysis, 41 treated tumors were contoured and 46 radiomic features were extracted. Results : The 1-year local control was 85.4% in our patient cohort, comparable with current results (87-99%). The Support Vector Machine (SVM) classifier, based on computed tomography (CT) scans in the A phase processed by equal probability (Ep) quantization with 8 gray levels, showed the highest mean F1 score (0.7995) for favorable LR within 1 year (W1R), at the end of follow-up (EndR), and condition of in-field failure-free (IFFF). The area under the curve (AUC) for this model was 92.1%, 96.3%, and 99.2% for W1R, EndR, and IFFF, respectively. Conclusions : SBRT has high 1-year local control and our study sets the basis for constructing predictive models for HCC patients receiving SBRT.

Background: Radiotherapy has gained increasing attention as an effective cytotoxic agent to improve therapeutic response to immunotherapy. However, synergic effect is seldom seen clinically and reliable biomarkers for optimal patient selection remains to be identified. Radiosensitivity index (RSI) is a well-known measure of tumor’s response to radiotherapy, which is derived from genomic data and system biology. Its association with the immune landscape in cancer is unclear. Methods: Genomic data from Merged Microarray-Acquired dataset (MMD) were established and the Cancer Genome Atlas (TCGA) were obtained. Based on rank-based regression model including 10 genes, RSI was calculated. A total of 12,832 primary tumors across 11 major cancer types were analyzed. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Gene set variance analysis was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. Findings: We found that RSI was significantly associated with homologous DNA repair, cancer stemness and various cancer-specific molecular features. Tumors with low RSI were associated with significantly higher portion of M1 macrophage, relative to M2 macrophage, and higher IFNG expression. Additionally, dominant interferon-γ (IFN-γ) response was characterized by low RSI and potentially predicted better response to programmed cell death 1 (PD-1) blockade. Interpretation: RSI is strongly associated with immune response and efficacy to PD-1 blockade. IFN-γ dominant status could be estimated by RSI, providing an alternative selection strategy to identify suitable patients for combined radiotherapy and immunotherapy. Funding Statement: This study was supported by study project of Tri-Service General Hospital (TSGH-D109063). Declaration of Interests: The authors declare that they have no competing interests.

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.

Background and purpose This study aimed to assess the incidence and risk of hypothyroidism among patients with nasopharyngeal carcinoma (NPC) after radiation therapy (RT). Material and methods We identified 14,893 NPC patients and 16,105 other head and neck cancer (HNC) patients treated with RT without thyroidectomy from the National Health Insurance Research Database in Taiwan between 2000 and 2011. Each NPC patient was randomly frequency-matched with four individuals without NPC by age, sex, and index year. Competing-risk regression models were used to estimate hazard ratios (HRs) of hypothyroidism requiring thyroxin associated with NPC after RT. Results The risk of developing hypothyroidism was significantly higher in the NPC cohort than in the matched cohort (adjusted HR=14.35, 95% CI=11.85–17.37) and the HNC cohort (adjusted HR=2.06, 95% CI=1.69–2.52). Independent risk factors for hypothyroidism among NPC patients included younger age, female sex, higher urbanization level, autoimmune disease, and receipt of chemotherapy. Conclusion The risk of hypothyroidism requiring thyroxin was significantly higher in NPC patients after RT than in the general Taiwanese population and HNC patients. Regular clinical and serum thyroid function tests are essential among NPC survivors after RT.

Objective: Previous case–control studies have suggested that women with migraine have lower risk of developing breast cancer, but conflicting results were noted in cohort studies. We investigated the association between migraine and breast cancer incidence in a nationwide population-based cohort study. Methods: We identified 25,606 women with migraine between 2000 and 2013 from the National Health Insurance Research Database in Taiwan. Each migraineur was randomly frequency matched with four women without migraine by age and index year of migraine diagnosis. Cox's proportional hazard regression analysis was performed to estimate the association between migraine on the risk of developing breast cancer. Results: With a mean follow-up of 7.3 years, 234 and 978 breast malignancies occurred in the migraine cohort and matched cohort, respectively. Migraine was not associated with the risk of breast cancer (adjusted hazard ratio = 1.03, 95% confidence interval = 0.89–1.21). Among women with migraine, in...

The locoregional failure rate remains high after concurrent chemoradiotherapy with standard-dose radiotherapy (RT, 50–50.4 Gy) for oesophageal cancer (EC). This retrospective study evaluated whether RT dose escalation was effective among 115 consecutive patients with non-metastatic EC (July 2003 to November 2016). Forty-four patients received an RT dose of

Skin injury is a major complication during radiation therapy and is associated with oxidative damage to skin cells. An effective and safe radioprotectant to prevent this skin damage is still unavailable. The Rhodiola crenulata root extract (RCE) has been reported to be a free radical scavenger and a potent anti-oxidant in both in vitro and in vivo models. In the current study, we investigated the effects of RCE on ionizing radiation-induced skin injury and its underlying mechanisms. HaCaT cells — a non-cancerous skin cell line together with HepG2, Caco2, A549, and OECM cancer cell lines — were pre-treated with RCE for 24[Formula: see text]h followed by exposure to 15 Gy using Caesium-137 as a γ-ray source. The cell viability was measured. In HaCaT cells, oxidative stress markers, cellular apoptosis pathways, matrix metalloproteinases (MMPs), and pro-inflammatory cytokine gene expression were studied. We found that RCE significantly protected HaCaT cells, but not cancer cells from the loss of viability induced by exposure to ionizing radiation. RCE attenuated radiation-induced oxidative stress markers, cell apoptosis, MMP levels, and expression of cytokine genes. RCE also limited the induction of p53 and p21 by radiation exposure. These findings indicate that RCE may selectively protect the skin cells from ionizing radiation without altering its ability to kill cancer cells. Therefore, we suggest that RCE or its derivatives could serve as a novel radioprotective therapy.

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.

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 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.

In early stage breast cancer, intraoperative radiation therapy (IORT) is a form of accelerated partial breast irradiation (APBI) that provides attractive therapeutic effects while shortening the overall treatment time and sparing the normal tissue radiation exposure. This technique has been used in Taiwan for several years in selected patients with breast cancer. However, some randomized trials pointed out that IORT is associated with higher rate of recurrence, therefore impeding its wider use as one of the standard managements in breast cancer. Also, despite its theoretical benefits for smaller tumor after surgery, the problem of recurrence warrants the necessity of strict and careful patient selection. The purpose of this article is to comprehensively review the updated consensus and current opinions on the use of IORT for early stage breast cancer.

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.

Background The purpose of this study was to assess the incidence and risk of depressive disorder among patients with head and neck cancer. Methods We identified 48 548 patients from the National Health Insurance Research Database (NHIRD) in Taiwan who were newly diagnosed with head and neck cancer between 2000 and 2010. Each patient was randomly frequency-matched with an individual without head and neck cancer, based on index year, sex, age, occupation category, urbanization level, monthly income, and comorbidities. The Cox proportional Registry of Catastrophic Illnesses Patient Database regression analysis was performed to estimate the effect of head and neck cancer on the risk of depressive disorder. Results Patients with head and neck cancer had a significantly higher risk of depressive disorder than the matched cohort (adjusted hazard ratio [HR] 3.32; 95% confidence interval [CI] 3.05-3.61), with the highest risk seen in the hypopharynx and oropharynx. Conclusion Patients with head and neck cancer had >3 times the incidence of depressive disorder, relative to the comparison group. Psychological evaluation and support are essential in head and neck cancer survivors.

Purpose The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. Methods From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. Results The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Conclusions Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

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.

We present an atypical case of cutaneous head and neck squamous cell carcinoma (cHNSCC), with parotid gland metastasis. This 56-year-old female presented with a slowly enlarging mass at the left pre-auricular region over the past year. At first, the patient described that there was only a bulging mass without apparent skin lesion or skin defect and it grew slowly. A magnetic resonance imaging (MRI) demonstrated a large lobulated lesion measuring 51 mm × 55 mm × 56 mm within the left parotid gland, which had invaded the ipsilateral masseter muscle causing displacement of the left lateral pterygoid muscle. The diagnostic radiologist made a provisional diagnosis of mucoepidermoid carcinoma (MEC) based on the finding of MRI. The patient then received left total parotidectomy with ipsilateral supraomohyoid neck dissection. The diagnosis later revised to cHNSCC with parotid lymph node metastasis based on pathological findings. cHNSCC may present solely as parotid tumor without apparent skin lesion which might also mimic primary MEC of the parotid gland.

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.

Aims and Background Recent clinical reports of stereotactic ablative radiotherapy (SABR) in the treatment of low-risk prostate cancer have been encouraging. Our study evaluates the efficacy and safety of SABR using the CyberKnife system for treating intermediate- to very-high-risk prostate cancer. Methods and Study Design Between May 2010 and June 2013, 31 patients (15 intermediate risk, 14 high risk, and 2 very high risk) without pelvic lymph node metastasis were enrolled retrospectively. The treatment consisted of 37.5 Gy in 5 fractions over 1-2 weeks using CyberKnife SABR. Twenty-five patients (81%) received androgen deprivation therapy (ADT). Biochemical failure was defined using the nadir + 2 criterion. Toxicity was assessed with the Common Terminology Criteria of Adverse Events (version 4). Results The median follow-up was 36 months (range 7-58 months). The median pretreatment prostate-­pecific antigen (PSA) was 13.5 ng/mL (range 4.5-124.0 ng/mL). The median PSA decreased to 0.09 ng/mL (range Conclusions Our preliminary results support that CyberKnife SABR with ADT is safe and feasible in patients with intermediate- to high-risk prostate cancer. A further large-scale clinical trial with longer follow-up is warranted.

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 present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. Methods and Materials: Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840–8200). In the once-daily regimen, RT was delivered using 180–200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560–8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. Results: The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria ( p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group ( p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively ( p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen ( p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. Conclusion: The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.

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.

前言：肝癌病人如有合併門靜脈腫瘤栓塞存活率相當差。近年來許多證據支持立體定位消融放射治療可當作肝癌病人治療選擇，但是極少文獻報導關於肝癌合併門靜脈腫瘤栓塞使用立體定位消融放射治療之臨床結果及預後因子。材料與方法：本研究以回溯性的方式，篩選西元 2008 年至 2013 年於本部接受立體定位消融放射治療之 42 位肝癌合併門靜脈腫瘤栓塞病人，本部立體定位消融放射治療之執行是使用電腦刀影像導引立體放射手術系統（Cyberknife image-guided radiosurgery system (AccurayInc., Sunnyvale, CA)）。所有病患接受之平均劑量為 42.5 Gy, 每次照射 5-12.5 Gy。臨床與治療相關的因子皆會詳細記錄，包括年齡、美國東岸癌症臨床研究合作組織（Eastern Cooperative Oncology Group）體能狀態、甲種胎兒蛋白數值、Child-Pugh score、Cancer of the Liver Italian Program (CLIP) score、有無肝外轉移（extrahepatic metastasis (EM)）等等。治療後會依據追蹤的影像評估腫瘤反應，影像上腫瘤反應之評估是依據 Response Evaluation Criteria in Solid Tumors (RECIST) 此一準則。存活率的分析是使用 Kaplan-Meier 法。預後因子的分析則是使用 Cox 比例風險模式。結果：追蹤時間中位數為 7.8 個月，共有 38 名病患死亡，中位數存活期為 8.6 個月，第一年及第二年的整體存活率分別是 31.4%及 14.1%。9 名病患在還沒接受治療後第一次影像追蹤即死亡。在有接受任何一次治療後影像學評估的病患當中，腫瘤完全反應率（complete response）是 3%，部分反應率（partial response） 是 55%，疾病穩定率（stable disease）是 39.1%，而病情惡化率（disease progression）是 3%。9 名（21%）病患門靜脈有被打通且有接受後續肝動脈化學栓塞療法（transarterial chemoembolization）。單變量分析發現 Child-Pugh A (vs. B & C, HR = 0.470, p = 0.049)、CLIP score ≤ 3 (vs. ＞ 3, HR = 0.468, p = 0.046) 以及無肝外轉移（vs. presence of EM, HR = 0.497, p = 0.035）的患者會有較佳的整體存活率。多變量分析則發現無肝外轉移（vs. presence of EM, HR = 0.340, p = 0.015）是唯一有統計學意義的預後因子。結論：立體定位消融放射治療，是肝癌合併門靜脈腫瘤栓塞病患的一個治療選擇；無肝外轉移是唯一可以預測較佳整體存活的獨立預後因子。

The aim of the article is to analyze breast cancer patient clinical outcomes after long-term follow-up using intensity-modulated radiotherapy (IMRT) or conventional tangential radiotherapy (cRT). We retrospectively reviewed patients with stage 0–III breast cancer who received breast conserving therapy between April 2004 and December 2007. Of the 234 patients, 103 (44%) were treated with IMRT and 131 (56%) were treated with cRT. A total prescription dose of 45 to 50 Gy (1.8–2 Gy per fraction) was delivered to the whole breast. A 14 Gy boost dose was delivered in 7 fractions. The median follow-up was 8.2 years. Five of 131 (3.8%) cRT-treated patients and 2 of 103 (1.9%) IMRT-treated patients had loco-regional failure. The 8-year loco-regional failure-free survival rates were 96.7% and 97.6% (P = 0.393) in the cRT and IMRT groups, respectively, whereas the 8-year disease-free survival (DFS) rates were 91.2% and 93.1%, respectively (P = 0.243). Patients treated with IMRT developed ≥ grade 2 acute dermatitis less frequently than patients treated with cRT (40.8% vs 56.5%; P = 0.017). There were no differences in late toxicity. IMRT reduces ≥ grade 2 acute skin toxicity. Local control, DFS, and overall survival were equivalent with IMRT and cRT. IMRT can be considered a standard technique for breast cancer treatment.

Background To analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy, and compare the results with patients treated with primary surgery. Methods Between January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT) using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method. Results The median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788). The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2) and pharyngitis (≥ grade 3) were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival. Conclusions IMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential.

Background: This study determines the pain-reducing effect of CyberKnife radiosurgery in the treatment of spinal lesions. Materials and Methods: We evaluated the clinical outcomes of patients treated with CyberKnife radiosurgery for spinal lesions in 65 patients with 76 spinal lesions at Tri-Service General Hospital, Taipei, Taiwan, from July 2007 to May 2013. Pre- and post-treatment visual analog scale (VAS) scores for pain were obtained. Results: In the benign cases, 12 patients had a pretreatment VAS score of 7 (46.2%); 12 patients, 8 (46.2%); and 2 patients, 9 (7.7%). For the posttreatment VAS scores, 10 patients had a score of 1 (38.4%); 15 patients, 2 (57.7%); and 1 patient, 4 (3.8%). In the malignant cases, 2 patients had a pretreatment VAS score of 8 (28.6%); 3 patients, 9 (42.9%); and 2 patients, 10 (28.6%). For the posttreatment VAS scores, 1 patient had a score of 2 (14.3%) and 6 patients had a score of 3 (85.7%). In the metastatic cases, 15 patients had a pretreatment VAS score of 8 (46.9%); 7 patients, 9 (21.9%); and 10 patients, 10 (31.3%). For the posttreatment VAS scores, 3 patients had a score of 1 (9.4%); 11 patients, 2 (34.4%); 16 patients, 3 (50%); and 2 patients, 4 (6.3%). Wilcoxon signed-rank tests to compare the pre- and post-treatment VAS scores in each patient group showed significant decreases in all groups (P < 0.05 for all comparisons). Conclusions: Collectively, these results show that significant pain relief without obvious adverse effects can be achieved when treating spinal lesions using stereotactic radiosurgery.

Background Patients with hepatocellular carcinoma (HCC) often have unresectable tumors. Transcatheter arterial chemoembolization (TACE) is one of the limited alternative treatments that can prolong these patients' survival. However, the presence of portal vein tumor thrombosis (PVTT) is a contraindication for TACE and, therefore, HCC patients with PVTT would be depleted of the advantage of TACE. The purpose of this study was to analyze the recanalization rate of thrombosed portal vein and treatment toxicities after stereotactic radiotherapy (SRT) or three-dimensional conformal radiotherapy (3DCRT). Methods From March 2002 to November 2004, 43 patients were enrolled in this prospective study. Twenty-two patients were in the SRT group and 21 in the 3DCRT group. For SRT, 3 Gy per fraction, 3 fractions per week, was given to a total dose of 45 Gy. For 3DCRT, a daily dose of 1.8 Gy, 5 fractions per week, was given to a total dose of 45 Gy. Results Of the 43 patients, 16 completed the planned radiotherapy. Eventually, 14 patients received evaluation for portal vein recanalization, 8 in the SRT and 6 in the 3DCRT group, respectively. For all patients, the crude response rate was 26%. For 14 evaluable patients, the crude response rate was 79%. It was 75% in the SRT group and 83% in the 3DCRT group (P = 0.71). The median survival time was 6.0 and 6.7 months for the SRT and 3DCRT group, respectively (P = 0.911). Conclusions Image-based radiotherapy, either SRT or 3DCRT, can recanalize the PVTT in unresectable HCC patients. Responders also had better 1 year and 2 year survivals. A more strict patient selection criterion may maximize the potential benefits of radiotherapy for hepatoma patients with PVTT.

Background. In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. Methods. During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. Results. The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1–2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. Conclusions. SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1–2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3–4 or N+ disease and should also be considered for patients with T1–2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005

Background: To analyze the local control of malignant lung tumors and survival of nonsmall cell lung cancer (NSCLC) patients after stereotactic ablative radiotherapy with CyberKnife. Materials and Methods: Patients with malignant lung tumors treated by CyberKnife between July 2007 and October 2010 at our institute were retrospectively reviewed. A total of 55 patients with 110 malignant lung tumors were included. There were 32 men and 23 women, and the median age was 67 years. There were 11 early-stage NSCLCs, while the other 44 patients with 99 lesions were metastatic lung tumors. The median gross tumor volume was 13.3 ml. Radiotherapy schedules include 40-60 Gy in 4-5 fractions, 45-60 Gy in 3 fractions and 30 Gy in 1 fraction. Results: The median follow-up time for patients alive was 34 months. The local control rates for all tumors were 96% at 1-year and 80% at 2 years. Univariate analysis demonstrated that target volume was important for local control. Biologically equivalent dose (BED) ≥100 Gy provided significantly higher chance to achieve a complete response than BED

Purpose: To report our observation of excessive temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients treated with 160 cGy b.i.d. radiotherapy technique. During the same period, patients treated with 120 cGy b.i.d. have not shown a similar tendency. Our experience may be useful for designing unconventional radiotherapy regimens for NPC patients. Methods and Materials: During the period from October 1991 to January 1998, 81 M0, previously untreated NPC patients completed altered fractionated radiotherapy. Seventy patients were treated with the hyperfractionated technique, and 11 were treated using the accelerated-hyperfractionated scheme. Hyperfractionated radiotherapy was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. A minimum tumor dose of 8000 cGy was the standard dose over an 8-week period. With the accelerated-hyperfractionated scheme, 160 cGy was given twice daily, also with an interval of 6 h. The minimum tumor dose ranged between 6840 and 7640 cGy, with 7 of the 11 patients receiving 7000 cGy. The arrangement of portals was the same for both regimens. The follow-up period for patients alive was from 32 to 102 months with a median of 61 months for the hyperfractionated patients. For the accelerated-hyperfractionated group, it ranged from 67 to 82 months with a median of 72 months. No patient was lost to follow-up. Results: At the time of analysis, 49 of the 70 patients in the hyperfractionated group were alive. In the accelerated group, 8 of the 11 patients were alive. The estimated radiation dose to the temporal lobe for the hyperfractionated group was 6000–7440 cGy with a median of 7080 cGy. For the accelerated-hyperfractionated group, the dose range was 4480–6700 cGy with a median of 6400 cGy. Of the 70 patients treated with hyperfractionated radiotherapy, none developed symptomatic brain necrosis, despite the higher total dose to the temporal lobe in general. In contrast, 3 of the 11 (27%) patients irradiated using the accelerated-hyperfractionated regimen suffered from temporal lobe necrosis at 16, 19, and 40 months after completion of radiotherapy. Conclusion: An excessive incidence of temporal lobe necrosis was noted when an accelerated-hyperfractionated regimen with 160 cGy b.i.d. was used in NPC patients with a median brain dose of 6400 cGy. There has been no such event in patients treated using a hyperfractionated regimen with 120 cGy and a median brain dose of 7000 cGy. The real causes of this discrepancy are not known. However, a high sensitivity of the human brain to a change in fraction size may play a role.