Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer.

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 ß-value from CpG probes based on sequencing with the Illumina Human 450 K platform. RESULTS: A high mean DNAm (ß > 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 < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway. CONCLUSIONS: Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

Skin Surface Dose for Whole Breast Radiotherapy Using Personalized Breast Holder: Comparison with Various Radiotherapy Techniques and Clinical Experiences.

PURPOSE: Breast immobilization with personalized breast holder (PERSBRA) is a promising approach for normal organ protection during whole breast radiotherapy. The aim of this study is to evaluate the skin surface dose for breast radiotherapy with PERSBRA using different radiotherapy techniques. MATERIALS AND METHODS: We designed PERSBRA with three different mesh sizes (large, fine and solid) and applied them on an anthropomorphic(Rando) phantom. Treatment planning was generated using hybrid, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques to deliver a prescribed dose of 5000 cGy in 25 fractions accordingly. Dose measurement with EBT3 film and TLD were taken on Rando phantom without PERSBRA, large mesh, fine mesh and solid PERSBRA for (a) tumor doses, (b) surface doses for medial field and lateral field irradiation undergoing hybrid, IMRT, VMAT techniques. RESULTS: The tumor dose deviation was less than five percent between the measured doses of the EBT3 film and the TLD among the different techniques. The application of a PERSBRA was associated with a higher dose of the skin surface. A large mesh size of PERSBRA was associated with a lower surface dose. The findings were consistent among hybrid, IMRT, or VMAT techniques. CONCLUSIONS: Breast immobilization with PERSBRA can reduce heart toxicity but leads to a build-up of skin surface doses, which can be improved with a larger mesh design for common radiotherapy techniques.

Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy.

In the era of immunotherapy, there lacks of a reliable genomic predictor to identify optimal patient populations in combined radiotherapy and immunotherapy (CRI). The purpose of this study is to investigate whether genomic scores defining radiosensitivity are associated with immune response. 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, radiosensitivity index (RSI) was calculated. A total of 12832 primary tumours across 11 major cancer types were analysed for the association with DNA repair, cellular stemness, macrophage polarisation, and immune subtypes. Additional 585 metastatic tissues were extracted from MET500. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Proteomic differential analysis was used to identify significant proteins according to RSI categories. Gene Set Variance Analysis (GSVA) was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. RSI was significantly associated with homologous DNA repair, cancer stemness and immune-related molecular features. Lower RSI was associated with higher fraction of M1 macrophage. Differential proteomic analysis identified significantly higher TAP2 expression in RSI-Low colorectal tumours. In the TCGA cohort, dominant interferon-γ (IFN-γ) response was characterised by low RSI and predicted better response to programmed cell death 1 (PD-1) blockade. In conclusion, in addition to radiation response, our study identified RSI to be associated with various immune-related features and predicted response to PD-1 blockade, thus, highlighting its potential as a candidate biomarker for CRI.

Stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the treatment of hepatocellular carcinoma with portal vein invasion: a retrospective analysis.

BACKGROUND: This study aimed to compare the clinical outcomes of stereotactic ablative radiotherapy (SABR) and conventionally fractionated radiotherapy (CFRT) in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). METHODS: HCC patients with PVI treated with radiotherapy from 2007 to 2016 were analysed. CFRT was administered at a median dose of 51.5 Gy (interquartile range, 45-54 Gy) with 1.8-3 Gy per fraction. SABR was administered at a median dose of 45 Gy (interquartile range, 40-48 Gy) with 6-12.5 Gy per fraction. Treatment efficacy, toxicity, and associated predictors were assessed. RESULTS: Among the 104 evaluable patients (45 in the SABR group and 59 in the CFRT group), the overall response rate (ORR, complete and partial response) was significantly higher in the SABR group than the CFRT group (62.2% vs. 33.8%, p = 0.003). The 1-year overall survival (OS) rate (34.9% vs. 15.3%, p = 0.012) and in-field progression-free survival (IFPS) rate (69.6% vs. 32.2%, p = 0.007) were also significantly higher in the SABR vs. CFRT group. All 3 rates remained higher in the SABR group after propensity score matching. Multivariable analysis identified SABR and a biologically effective dose ≥65 Gy as favourable predicators of OS. There was no difference between treatment groups in the incidence of radiation-induced liver disease or increase of Child-Pugh score ≥ 2 within 3 months of radiotherapy. CONCLUSIONS: SABR was superior to CFRT in terms of ORR, OS, and IFPS. We suggest that SABR should be the preferred technique for HCC patients with PVI.

Definitive radiotherapy dose escalation with chemotherapy for treating non-metastatic oesophageal cancer.

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 <66 Gy and 71 patients received ≥66 Gy, with most patients receiving concurrent cisplatin plus fluorouracil. The median follow-up was 12 months for all patients (52 months for 18 surviving patients). The ≥66 Gy group had significantly higher 3-year rates of overall survival (17.9% vs. 32.1%, p = 0.026) and local progression-free survival (46.1% vs. 72.1%, p = 0.005), but not disease progression-free survival (11.4% vs. 21.9%, p = 0.059) and distant metastasis-free survival (49% vs. 52.6%, p = 0.852). The ≥66 Gy group also had significantly better 5-year overall survival compared with 41.4-65.9 Gy. The only significant difference in treatment-related toxicities involved acute dermatitis (7% vs. 28%, p = 0.009). Inferior overall survival was associated with poor performance status, clinical N2-3 stage and not receiving maintenance chemotherapy. In conclusion, patients with inoperable EC experienced better survival outcomes and acceptable toxicities if they received higher dose RT (≥66 Gy) rather than lower dose RT (<66 Gy).

Rhodiola crenulata Attenuates γ-Ray Induced Cellular Injury via Modulation of Oxidative Stress in Human Skin Cells.

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.

Risk of depressive disorder among patients with head and neck cancer: A nationwide population-based study.

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.

Association Between Migraine and Breast Cancer Risk: A Population-Based Cohort Study and Literature Review.

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, independent risk factors for breast cancer included older age, alcohol-related illness, and receipt of a greater number of breast cancer screening examinations, and independent protective factors included the use of antihypertensive agents, statins, and nonsteroidal anti-inflammatory drugs. Further analyses indicated that women with ≥4 medical visits for migraine per year had a significantly greater risk of breast cancer than the matched cohort. Conclusions: Migraine was not associated with a decreased risk of developing breast cancer among Taiwanese women. Further prospective studies on other geographic populations or on the association between migraine frequency and the risk of developing breast cancer are warranted to validate our findings.

Association between nasopharyngeal carcinoma and risk of optic neuropathy: A population-based cohort study.

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.

Comparison Between Child-Turcotte-Pugh and Albumin-Bilirubin Scores in Assessing the Prognosis of Hepatocellular Carcinoma After Stereotactic Ablative Radiation Therapy.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.

Risk of hypothyroidism among patients with nasopharyngeal carcinoma treated with radiation therapy: A Population-Based Cohort Study.

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.

Survival and prognostic factors for patients with advanced hepatocellular carcinoma after stereotactic ablative radiotherapy.

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 <0.001). CONCLUSIONS: SABR may be useful for patients with advanced HCC, and patient selection could be based on the CTP classification, main portal vein tumor thrombosis, and extrahepatic spread.

Lower Urinary Tract Infection and Subsequent Risk of Prostate Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: We investigated whether lower urinary tract infection (LUTI), including cystitis or urethritis, is associated with an increased risk of developing prostate cancer (PCa), in a nationwide population-based cohort study. METHODS: We identified 14,273 men newly diagnosed with LUTI (9347 with cystitis, and 4926 with urethritis) between 1998 and 2011, from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with 4 men without LUTI, based on age and index year of diagnosis. Cox's proportional hazard regression analysis was performed to estimate the effect of LUTI on the PCa risk. RESULTS: The risk of developing PCa was significantly higher in the cystitis cohort (adjusted HR = 1.46, 95% CI = 1.20-1.78) and in the urethritis cohort (adjusted HR = 1.72, 95% CI = 1.26-2.34) than in the group without LUTI. Further analyses indicated that patients with more than 5 medical visits for LUTI per year had a significantly greater risk of developing PCa. CONCLUSION: We found that cystitis or urethritis may play an etiological role in the development of PCa in Taiwanese men, particularly in those with repeated medical visits for cystitis or urethritis. Further studies are warranted on the association between LUTI and PCa in other countries, particularly where the prevalence of PCa is high.

Stereotactic ablative radiotherapy for patients with unresectable or medically inoperable cholangiocarcinoma.

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.

Dose escalation via brachytherapy boost for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy and combined chemotherapy.

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.

Long-Term Breast Cancer Patient Outcomes After Adjuvant Radiotherapy Using Intensity-Modulated Radiotherapy or Conventional Tangential Radiotherapy.

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.

Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy.

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.

Comparing outcomes of stereotactic body radiotherapy with intensity-modulated radiotherapy for patients with locally advanced unresectable pancreatic cancer.

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.

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results.

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 <0.04-5.38 ng/mL) and 0.12 ng/mL (range <0.04-2.63 ng/mL) at 6 months and 12 months after SABR, respectively. The 3-year biochemical relapse-free survival was 90.2% for all patients, 100% for the intermediate-risk patients, and 82% for the high- and very-high-risk patients (p = 0.186). No patient experienced ≥ grade 3 toxicity. There were 7 acute and 5 late grade 2 genitourinary toxicities and 1 acute and no late grade 2 gastrointestinal toxicity. 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.

Dose escalation using twice-daily radiotherapy for nasopharyngeal carcinoma: does heavier dosing result in a happier ending?

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.