Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology. METHODS: Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models. RESULTS: The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable. CONCLUSIONS: Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment.

Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A-Bora complex.

Pin1 was the first prolyl isomerase identified that is involved in cell division. The mechanism by which Pin1 acts as a negative regulator of mitotic activity in G2 phase remains unclear. Here, we found that Aurora A can interact with and phosphorylate Pin1 at Ser16, which suppresses the G2/M function of Pin1 by disrupting its binding ability and mitotic entry. Our results also show that phosphorylation of Bora at Ser274 and Ser278 is crucial for binding of Pin1. Through the interaction, Pin1 can alter the cytoplasmic translocation of Bora and promote premature degradation by ß-TrCP, which results in a delay in mitotic entry. Together with the results that Pin1 protein levels do not significantly fluctuate during cell-cycle progression and Aurora A suppresses Pin1 G2/M function, our data demonstrate that a gain of Pin1 function can override the Aurora-A-mediated functional suppression of Pin1. Collectively, these results highlight the physiological significance of Aurora-A-mediated Pin1 Ser16 phosphorylation for mitotic entry and the suppression of Pin1 is functionally linked to the regulation of mitotic entry through the Aurora-A-Bora complex.

HyperArcTM volumetric modulated arc therapy for hypopharyngeal cancer with solitary recurrence in the cervical vertebra: A case report and literature review.

RATIONALE: It is difficult to reirradiate head and neck cancers because of the toxicity from previous radiation dose delivery. Conventional volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy often have poor target coverage. The new HyperArcTM VMAT (HA-VMAT) planning approach reportedly has better target coverage, higher conformity, and can spare normal organs compared to conventional VMAT; however, research on recurrent head and neck cancers is limited. Here, we report the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence in the first cervical vertebra (C1). PATIENT CONCERNS: A 52-year-old Asian male was diagnosed with a hypopharyngeal cancer. The patient received concurrent chemoradiotherapy with a radiation dose of 70 Gy in 33 fractions and achieved complete clinical response. Two years later, solitary recurrence was observed in the C1 vertebra. DIAGNOSES: Solitary recurrence in the C1 vertebra. INTERVENTIONS: Owing to concerns regarding the toxicity to adjacent organs, we decided to use HA-VMAT to achieve better tumor coverage and critical organ sparing. OUTCOMES: Tumor regression was observed on the imaging. At 9 months follow-up, the patient was disease-free and had no late toxicities. LESSONS: This is the first report regarding the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence over the C1 vertebra. HA-VMAT achieves highly conformal dose distribution and excellent sparing of critical organs. There was a favorable initial clinical response with no toxicity. Long-term follow-up is essential in such cases.

Challenges of BCLC stage C hepatocellular carcinoma: Results of a single-institutional experience on stereotactic body radiation therapy.

In this study, we evaluated the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).This retrospective study evaluated 139 patients with BCLC stage C HCC who underwent CyberKnife SBRT between January 2009 and September 2017. All patients had BCLC-C, Child-Turcotte-Pugh score A-B. In-field control, overall survival (OS), progression free survival (PFS), and prognostic factors were evaluated.An objective response rate was achieved in 81.5% patients (complete response, 36.2%, partial response, 45.3%). The median survival was 15.44 months, and the 1-, 3-, 5-year OS rates were 56%, 28%, and 20%, respectively. The median PFS was 6 months, the PFS rate at 1-, 3-, and 5-year were 35%, 14%, and 10%, respectively. In-field control of 1 to 2 years was achieved in 85.1% of patients. The major pattern of failure was out-field intrahepatic failure which comprised 42.9% of patients. Multivariate analysis revealed that the Child-Turcotte-Pugh score, macrovascular invasion, advance stage (III-IV), and tumor response rate were independent predictors of OS.The result of our study shows that SBRT is a safe and effective therapeutic option for BCLC stage C HCC lesions that are unsuitable for standard loco-regional therapies, Moreover, SBRT has acceptable local control rates and low-treatment toxicity.

Comparison of stereotactic body radiation therapy with and without sorafenib as treatment for hepatocellular carcinoma with portal vein tumor thrombosis.

Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for unresectable hepatocellular carcinoma (HCC) patients. However, the treatment outcomes for patients with portal vein tumor thrombosis (PVTT) remain poor. In this study, we evaluate the efficacy of SBRT with and or without sorafenib for advanced HCC with PVTT.Fifty four HCC patients with PVTT treated with SBRT using the Cyberknife system was retrospectively analyzed between January 2009 and June 2016. Of these, sorafenib combined with SBRT was administered to 18 patients and SBRT alone was administered to 36 patients. SBRT was designed to target the liver tumor and tumor thrombosis, with a radiation dose of 36 to 45 Gy (median 40 Gy) given in 3 to 5 fractions.The mean follow-up period for SBRT with sorafenib and SBRT alone was 13.22 ±â€Š10.07 months and 15.33 ±â€Š22.01 months, respectively. The response rate was comparable in both groups. Complete response and partial response rates were 77.77% for SBRT with sorafenib and 75.00% without sorafenib (P = .43). The median progression-free survival rate was 6 months (2-11 months) versus 3 months (2-5.6 months) (P = .24) and the 1- and 2-year progression-free survival rates were 25.7% and 15.2% versus 11.1% and 8.3% (P = .1225). The median, 1- and 2-year overall survival rates (OSR) were 12.5 months, 55.6% and 17.7% versus 7 months (5-13.5 months), 33.3% and 11.1% (P = .28), for SBRT with sorafenib versus SBRT alone groups, respectively.The result of our study shows that SBRT with sorafenib administered group resulted in a higher median, progression-free, and OSR for HCC patients with PVTT. However, the trends did not attain statistical significance. A large-scale randomized study is needed to assess the benefits of SBRT with sorafenib administration for patient with PVTT.

Development and Validation of a Nomogram for Patients with Nonmetastatic BCLC Stage C Hepatocellular Carcinoma after Stereotactic Body Radiotherapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for hepatocellular carcinoma (HCC) with promising outcome. However, appropriate survival prediction models are scarce. This study aimed to develop a simple and clinically useful prognostic nomogram for patients with nondistant metastatic Barcelona Clinic Liver Cancer (BCLC) stage C HCC undergoing SBRT. METHODS: The data were based on a prospective multi-institutional registry enrolling 246 patients with nondistant metastatic BCLC stage C HCC treated with SBRT between January 1, 2008 and December 31, 2016. They were randomly divided into two subsets: 164 into the development cohort and 82 into the validation cohort. We identified and included prognostic factors for survival to derive a nomogram in the development cohort. The predictability of the nomogram was evaluated in the validation cohort. The area under the receiver operating characteristic curve (AUROC) and the calibration plot were used to evaluate the performance of the nomogram. RESULTS: The median survival was 13.5 months, with 1- and 2-year overall survival (OS) rates of 55.0 and 32.9%, respectively. Number of tumors, largest tumor size, macrovascular invasion, Child-Turcotte-Pugh class, and biologically effective dose were significantly associated with OS (p < 0.05). These predictors were included to develop a nomogram with an AUROC of 0.77 (0.73-0.87). The prediction model was well calibrated in the validation cohort. The OS for patients who were divided by their risk scores differed significantly (p < 0.001). CONCLUSIONS: The nomogram we generated had discriminatory and satisfactory predictability for OS among nonmetastatic BCLC stage C HCC patients treated with SBRT. It demands further validations with cross-country data to confirm its worldwide usefulness.

A seven-year experience of using moderate deep inspiration breath-hold for patients with early-stage breast cancer and dosimetric comparison.

We present our seven-year experience of using moderate deep inspiration breath-hold (mDIBH) with an active breathing control (ABC) device for patients with early-stage breast cancer and dosimetric comparison to evaluate the benefit of mDIBH on the heart, lung, and liver.We retrospectively reviewed all patients with newly diagnosed breast cancer and having clinical stage Tis, I, or II disease treated between November 2010 and October 2017. Among the 369 patients included in this study, 107 patients were treated with mDIBH and 262 patients were treated with free breathing (FB). Dosimetric analysis was performed to compare dose distribution in the heart, lung, and liver between the two treatment groups. The chi-square test was used to compare the distribution of stage and tumor site between the two groups. The independent samples t-test was used to compare the remaining parameters between the two groups.For all 369 patients, there was a significantly lower ipsilateral lung V5 (relative volume receiving ≧5 Gy), ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose in the mDIBH group. For 184 patients with a left-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose were observed in the mDIBH group. For 185 patients with a right-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, mean heart dose, liver V30, and mean liver dose were observed in the mDIBH group.For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver.

Effects of zinc supplementation on clinical outcomes in patients receiving radiotherapy for head and neck cancers: a double-blinded randomized study.

PURPOSE: To evaluate the impact of zinc supplementation on the survival of patients after receiving radiotherapy for head and neck cancers. METHODS AND MATERIALS: Patients were randomly divided into two groups; experimental and control. Patients in the experimental group received a predetermined dose of a zinc supplement, and the control group, a placebo. The 50 patients in each group could be considered homogenous with respect to medical histories, tumor characteristics, and therapeutic details. RESULTS: Patients in both groups appeared to have similar results for 3-year overall, disease-free, and metastases-free survival rates (p = 0.19, p = 0.54, and p = 0.35, respectively). However, patients in the experimental group had better 3-year local-free survival (LFS), although the difference was only marginal (p = 0.092). Another difference was that patients in the experimental group with Stages III-IV disease had a much better 3-year LFS rate when they received concurrent chemoradiotherapy (p = 0.003). CONCLUSIONS: One impact seen was that zinc supplementation improved LFS at 3 years after beginning treatment for patients with Stages III-IV disease. It is imperative that these patients be followed up for a longer period to draw a definite conclusion.

Evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma: A single institution experience.

The optimal radiation dose for definitive chemoradiotherapy in inoperable esophageal squamous cell carcinoma (ESCC) has been long debated. In this study, we evaluated the effect of doses greater than the conventional radiation dose (50.4 Gy) on tumor control, tumor response, overall survival (OS), and disease-free survival (DFS).The database of patients diagnosed with inoperable ESCC from 2007 to 2015 was obtained from the cancer registry of Chi-Mei Medical Center. All categorical variables were compared using Chi-squared test. The risk of OS and DFS were estimated using Cox proportional hazards regression, and Kaplan-Meier plots presented the trend of OS and DFS with log-rank tests used to compare differences. All significance levels were set at P < .05.A total of 84 patients were retrospectively analyzed, with 42 (50%) receiving >50.4 Gy and 42 (50%) receiving ≤50.4 Gy (50%) concurrently with chemotherapy. Univariate and multivariate analysis revealed no significant differences between higher dose and conventional dose in OS (P = .21) and DFS (P = .26). Further dose analysis of <50, 50 to 50.4, 51 to 60, and >60 Gy showed no significant differences in OS or DFS. Higher doses conveyed no significant benefit on the failure pattern, either local regional failure or distant failure (P = .42). Major prognostic factors associated with better OS on multivariate analysis were stages I and II patients (P = .03) and radiation technique using arc therapy (P = .04). No acute toxicity of grade III or higher was recorded.The results of our study show that providing higher than conventional radiation doses concurrent with chemotherapy for inoperable ESCC does not impact OS or DSF, nor does it improve locoregional failure or distant failure. Although tumor response might be improved by radiation doses >50.4 Gy, the impact on OS and DFS remain to be studied.

The age-adjusted Charlson comorbidity index is a better predictor of survival in operated lung cancer patients than the Charlson and Elixhauser comorbidity indices.

OBJECTIVES: To compare the prognostic performance between different comorbidity assessments of survival in patients with operated lung cancer. METHODS: A total of 4508 lung cancer patients treated by surgery between 2003 and 2012 were identified through Taiwan's National Health Insurance Research Database. Information on pre-existing comorbidities prior to the cancer diagnosis was obtained and adapted to the Charlson comorbidity index, age-adjusted Charlson comorbidity index (ACCI) and Elixhauser comorbidity index scores. The influence on survival was analysed using a Cox proportional hazard model. The discriminatory ability of the comorbidity indices were evaluated using Akaike information criterion and Harrell's C-statistic. RESULTS: The mean age of the study cohort was 64.95 ± 11.15 years, and 56.28% of the patients were male. The median follow-up time was 2.59 years, and the 3-year overall survival was 73.94%. Among these patients, 2134 (47.3%) patients received adjuvant therapy. The Charlson comorbidity index and ACCI scores correlated well with survival and higher scores were associated with an increased 3-year mortality risk (hazard ratio = 1.21, 95% confidence interval = 1.03-1.42 and hazard ratio = 1.43, 95% confidence interval = 1.08-1.90, respectively) in multivariate analysis. The ACCI scores provided better discriminatory ability with a smaller Akaike information criterion and greater Harrell's C-statistic for 3-year overall survival compared to the Charlson comorbidity index or Elixhauser comorbidity index scores. CONCLUSIONS: The operated lung cancer patients with severe comorbidities were associated with worse survival. The ACCI appears to be a more appropriate prognostic indicator and should be considered for use in clinical practice.

Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma.

Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT.Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4-<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed.A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival.SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate.

Hyperlipidemia and statins use for the risk of new-onset anxiety/depression in patients with head and neck cancer: A population-based study.

OBJECTIVE: Anxiety/depression is common among patients with head and neck cancer (HNC), and can negatively affect treatment compliance and outcome. The aim of this study was to assess the association between hyperlipidemia and the risk of new-onset anxiety/depression after the diagnosis of HNC and the influence of administering statins. METHODS: A matched longitudinal cohort study of 1632 subjects (408 HNC patients with preexisting hyperlipidemia and 1224 age- and sex-matched HNC patients without hyperlipidemia) was included and analyzed by using data from Taiwan's National Health Insurance Research Database from January 1996 to December 2012. The incidence and hazard ratios (HRs) for the development of new-onset anxiety/depression were examined between the two groups. Cox proportional hazard regression was applied to estimate the relative risks of anxiety/depressive disorders adjusted for potential confounding factors. To estimate the risks of anxiety/depression in different sub-groups, a stratified analysis was also used. RESULTS: HNC patients with preexisting hyperlipidemia had a higher risk for comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease (P <0.001). The incidence rate of anxiety/depression in the HNC patients with preexisting hyperlipidemia was also significantly higher than that among patients without hyperlipidemia (10.78% vs 7.27%, respectively; P = 0.03). A Cox regression model revealed that preexisting hyperlipidemia was an independent risk factor for anxiety/depression (aHR, 1.96; 95% CI, 1.30-2.94). Statins use was protective against anxiety/depression among HNC patients with hyperlipidemia (aHR, 0.85; 95% CI, 0.46-1.57), especially for individuals older than 65 years and for females. CONCLUSIONS: Preexisting hyperlipidemia was associated with increased risk of new-onset anxiety/depression in the HNC patients. Statins use for HNC patients with hyperlipidemia could decrease the risk of anxiety/depression, especially for those older than 65 years and for female patients.

Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study.

PURPOSE: To determine whether zinc supplementation can accelerate the healing of mucositis and dermatitis after radiotherapy. METHODS AND MATERIALS: In this double-blind study, patients were placed into two randomized groups (experimental and control) of 50 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The experimental group received a standard dose of a zinc supplement, and the control group was given a placebo. RESULTS: Patients in the control group developed Grade 2 mucositis and dermatitis earlier and sooner than patients in the experimental group. There was also a significant difference in the development of Grade 3 mucositis and dermatitis between the two groups. Patients in the experimental group were found to have milder mucositis and dermatitis. Zinc supplementation did not show much benefit in those patients receiving concurrent chemotherapy or make a substantial impact on weight changes. CONCLUSIONS: Zinc supplementation used in conjunction with radiotherapy could postpone the development of severe mucositis and dermatitis for patients with cancers of the head and neck. Zinc supplementation can also alleviate the degree of mucositis and dermatitis. The impact of zinc on tumor growth and patient survival is under further investigation.

p53 and p27 as predictors of clinical outcome for rectal-cancer patients receiving neoadjuvant therapy.

Our aim was to examine whether certain molecular markers, specifically p53, p21, p27, and Bcl-2, could be used to predict the tumor response of rectal cancer to neoadjuvant therapy and determine the overall and disease-free survival rates of patients following neoadjuvant therapy. Seventy-seven patients with rectal cancers were used in this study. All of them received neoadjuvant therapy and 53 of them were given radical surgery. Immunohistochemical tests were performed for the four markers mentioned above using biopsy specimens obtained from 70 of the patients prior to radiation. The identical tests were performed for the same markers using excised specimens from the patients after radical surgery. For the pre-radiation specimens, the positive rate for having p27 and Bcl-2 markers was 32.7% and 16.6%, respectively. This rate increased to 73.5% and 41.6% (p=0.001 and 0.012, respectively) in the specimens obtained after the surgery. With respect to "fair response (FR)" of patients, the pre-radiation biopsy specimens showed significant difference for the p53 (-) and p27 (+) markers (p=0.006). Patients with a 3-year overall survival rate were found to have, from their surgical specimens, 92% of the p27 (+) and 75% of p27 (-) markers (p=0.0058). Our study showed: first, the rate of positive identification of molecular markers, p27 and Bcl-2, increased following neoadjuvant therapy. Second, either the p53 (-) or p27 (+) status was a good predictor for FR in the pre-radiation biopsy specimens. Third, patients with p27 (+) markers in the surgical specimens lived longer at 3 years.

Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy.

PURPOSE: To investigate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cervical cancer and their association with clinical outcome in patients treated with radical radiotherapy. METHODS AND MATERIALS: One hundred sixty-seven consecutive patients with FIGO Stages IB-IVA squamous cell cervical cancer underwent radical radiotherapy, including external-beam radiotherapy or high-dose-rate brachytherapy, or both, between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and evaluate the effects of the factors affecting patient survival. RESULTS: Positive immunostainings of iNOS and COX-2 were observed in 58.7% and 64.1% of the participants, respectively. The expression of both iNOS and COX-2 was positively correlated (Spearman correlation coefficient = 0.49, p < 0.01), and their overexpression provided independent predictors of distant metastasis (odds ratio = 5.22 and 10.07, respectively; p < 0.01 for all). iNOS- and COX-2-expressing patients had significantly shorter disease-free survival (p < 0.01, both) and cause-specific overall survival (p = 0.01, p < 0.01, respectively). Patients with iNOS-positive/COX-2-positive tumors had the poorest survival rates. Coexpression of iNOS/COX-2, together with bulky tumor and advanced stage were independent prognostic factors for disease-free survival. CONCLUSION: Overexpression of iNOS or COX-2 or both was associated with decreased survival and a greater propensity to metastasize in cervical cancer patients treated with radiotherapy. Coexpression of iNOS and COX-2 may represent a useful biologic marker in patients receiving radical radiotherapy for cervical cancer.

Comprehensive measurement for clinical dosimetry of tertiary multileaf collimator.

To initiate the use of a tertiary multileaf collimator (MLC) in the clinic, a set of dosimetry data for clinical use of the MLC, the secondary field size jaw and the MLC tracked by the jaw were measured. The dose calculation technique from the commissioned jaw field data was established. The dosimetry characteristics included absolute output (Dw), collimator scatter factor (Sc), total scatter factor (Scp), phantom scatter factor (Sp), percentage depth dose (PDD), tissue-maximum ratio (TMR), and peak scatter factor (PSF). The absolute output of the MLC field was +5% to +2% greater than that of the same jaw size field from 4 x 4 to 24 x 24 cm2 fields. The variation of Sc and Scp ranged from 4 x 4 to 24 x 24 cm2 fields and were less than that of the jaw fields, while the Sp, PDD and TMR values remained the same. Importantly, when the MLC-only field was performed without the collimator jaws tracking close to the field segments, greater output was delivered, and PSFs should be used to calculate the MLC field output.

The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities.

BACKGROUND AND AIM: To evaluate the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other standard treatment option. METHODS: Between 2009 and 2011, 22 patients with unresectable huge HCC (≧10 cm) were treated with SBRT. dose ranged from 26 Gy to 40 Gy in five fractions. Overall survival (OS) and disease-progression free survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and toxicities were also assessed. RESULTS: After a median follow-up of 11.5 month (range 2-46 months). The objective response rate was achieved in 86.3% (complete response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2-46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose (p = 0.0017) were significant factors for survival. However, in multivariate analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child-Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild and well tolerated. CONCLUSION: This study showed that SBRT can be delivered safely to huge HCC and achieved a substantial tumor regression and survival. The results suggest this technique should be considered a salvage treatment. However, local and regional recurrence remain the major cause of failure. Further studies of combination of SBRT and other treatment modalities may be reasonable.

A novel long-acting analgesic: buprenorphine palmitate in rats.

BACKGROUND: A long-acting analgesic may be particularly desirable in patients with long-lasting pain. In order to provide a long-acting analgesic effect, a novel buprenorphine ester, buprenorphine palmitate, was synthesized in our laboratory. The aim of the study was to evaluate whether the ester had a long-lasting effect. METHODS: The antinociceptive effects (dose-range studies) of buprenorphine HCl and buprenorphine palmitate were evaluated using the plantar test in Sprague-Dawley rats. RESULTS: We found that intramuscular injection of buprenorphine HCl 0.05, 0.1 and 1 micromol/kg in rats produced dose-related antinociceptive effects of 2, 3, and 4 h, respectively. Intramuscular injection of buprenorphine palmitate 1, 5, and 10 micromol/kg also produced dose-related antinociceptive effects of 72, 76 and 78 h, respectively. On an equimolar basis of 1 micromol/kg, the durations of action of intramuscular buprenorphine HCl and buprenorphine palmitate were 4 and 72 h, respectively. CONCLUSIONS: Intramuscular injection of buprenorphine palmitate in rats produced a long-lasting antinociceptive effect which was much longer (18-fold) than did intramuscular buprenorphine HCl.

Primary brain lymphoma: a report of eight cases from a medical center in southern Taiwan.

BACKGROUND: Primary brain lymphoma (PBL) in Taiwan has been reported only in three series with very limited immunophenotypic characterization. METHODS: We retrospectively studied PBL cases with history review, immunohistochemistry, and in situ hybridization (ISH) for Epstein-Barr virus-encoded mRNA (EBER) from a single institution in southern Taiwan during 1989-2000. RESULTS: We found eight cases of PBL including four males and four females with mean age of 64.1 years and median of 63.0. The major presenting symptoms were headache, poor memory, slurred speech, and hemiplegia in three patients each. All patients had stage I solitary tumor. Half of the patients received tumor excision, the other half, stereotactic biopsy. Seven cases were of diffuse large B-cell type (DLBL), with expression of bcl-2 in six cases. They were all negative for CD5, CD10, bcl-6, and EBER. The eighth patient had anaplastic large cell lymphoma (ALCL) of T-cell phenotype with expression of cytotoxic markers and was positive for EBER. Two were lost to follow up. The median follow-up time for the remaining six was 11.2 months (range, 5.5 - 25.0). They all received radiotherapy with initial complete remission. Two died of the disease, another of cardiopulmonary failure, and the other of stroke or recurrence. The remaining two were free of disease for 9.6 and 25.0 months after radiotherapy alone. The 1-year survival rate was 60%. CONCLUSIONS: We have fully characterized eight cases of PBL, including seven DLBLs and one ALCL, in southern Taiwan that occurred in an older age group. Old age, immunophenotype (bcl-2-positivity and bcl-6-negativity), and lack of systemic chemotherapy were probably responsible for the shorter survival as compared to other studies. Radiotherapy seems to be effective for inducing complete remission and even long-term survival in some patients, however, systemic chemotherapy should be administered to prevent recurrence and to achieve long-term survival.