Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). METHODS: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed. RESULTS: 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT. CONCLUSIONS: SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

Sources of exposure to urinary phthalates among couples undergoing infertility treatment.

Phthalates have been implicated as reproductive toxicants in animal models and in human populations. This study examined associations between potential exposure sources and urinary phthalate metabolite concentrations among women (n = 56) and their male partners (n = 43) undergoing in vitro fertilization (IVF). On the day of oocyte retrieval, participants provided urine samples and completed questionnaires detailing use of personal care products (PCPs), and consumption of medications, foods, and beverages in the preceding 24 h. Urine was analyzed for MEP, MBP, MPP, MHxP, MEHP, MEHHP, MECPP, MiNP, MiDP, MCHP, and MBzP, via liquid chromatography-tandem mass spectrometry. We employed principal component analysis (PCA) to summarize exposure sources and regression models to estimate associations between exposure patterns and urinary phthalate metabolites, adjusted for confounding variables. Among women, application of more body washes and eye creams, and consumption of more supplements, was associated with greater urinary MECPP [relative difference = 1.36 (95% CI: 1.28, 1.45)] and the molar sum of DEHP metabolites, including MEHP, MEHHP, and MECPP [∑DEHP; 1.26 (95% CI: 1.17, 1.34)]. Among men, consumption of more supplements and allergy medications was associated with greater urinary MECPP, MEHHP, and ∑DEHP [relative difference = 1.13 (95% CI: 1.02, 1.23)] concentrations. Identifying differences in sources of phthalate exposure may help clinicians to intervene to reduce exposure as part of a comprehensive strategy to help improve IVF outcomes.

Depressive Symptoms, Co-Morbidities, and Glycemic Control in Hong Kong Chinese Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Undiagnosed depression is an important comorbidity in type 2 diabetes (T2D) which can be detected using the Geriatric Depression Scale (GDS-15) questionnaire. In this cross-sectional study, we examined the associations of depression using GDS score with control of cardiometabolic risk factors and health status in elderly patients with T2D. SETTING AND PARTICIPANTS: Between February and December 2013, patients aged ≥65 years who underwent structured comprehensive assessment as a quality improvement program at the Diabetes Center of a teaching hospital were invited to complete the GDS-15 questionnaire. MAIN OUTCOME MEASURES: Depression was defined as a GDS score ≥7. Demographic data, prior history of co-morbidities, frequency of self-reported hypoglycemia, and attainment of treatment targets defined as HbA1c, <7%, blood pressure <130/80 mmHg, and LDL-C <2.6 mmol/L were documented. RESULTS: Among 325 participants (65% male, median [interquartile range] age: 69 [8] years), 42 (13%) had depression. Patients with depression had longer disease durations (mean ± SD: 15.1 ± 9.1 vs. 11.6 ± 8.1 years, P = 0.02), more frequent self-reported hypoglycemic events (17 vs. 6%, P = 0.03) and were less likely to attain all three treatment targets (0 vs. 16%, P = 0.004) than those without depression. On multivariable analysis, patients with depression had an odds ratio of 2.84 (95% confidence intervals: 1.35-6.00, P = 0.006) of reporting prior history of co-morbidities. CONCLUSION: In elderly patients with T2D, depression was not uncommon especially in those with poor control of risk factors, hypoglycemia, and co-morbidities. Inclusion of GDS-15 questionnaire during structured assessment for complications and risk factors can identify these high-risk patients for more holistic management of their physical and mental health.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma.

PURPOSE: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). METHODS AND MATERIALS: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. RESULTS: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). CONCLUSIONS: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG.

BACKGROUND: Postoperative chemoradiation and perioperative chemotherapy using epirubicin/cisplatin/5-fluorouracil (ECF) represent two standards of care for resectable gastric cancer. In the TOPGEAR (Trial Of Preoperative therapy for Gastric and Esophagogastric junction AdenocaRcinoma) trial, we hypothesized that adding preoperative chemoradiation to perioperative ECF will improve survival; however, the safety and feasibility of preoperative chemoradiation have yet to be determined. METHODS: TOPGEAR is an international phase III trial in which patients with adenocarcinoma of the stomach were randomized to perioperative ECF alone or with preoperative chemoradiation. The ECF-alone group received three preoperative cycles of ECF, while the chemoradiation group received two cycles of preoperative ECF followed by chemoradiation. Both groups received three postoperative cycles of ECF. A planned interim analysis of the first 120 patients was conducted, and was reviewed by the Independent Data Safety Monitoring Committee to assess treatment compliance, toxicity/safety, and response rates. RESULTS: The proportion of patients who received all cycles of preoperative chemotherapy was 93% (ECF group) and 98% (chemoradiation group), while 65 and 53%, respectively, received all cycles of postoperative chemotherapy. Overall, 92% of patients allocated to preoperative chemoradiation received this treatment. The proportion of patients proceeding to surgery was 90% (ECF group) and 85% (chemoradiation group). Grade 3 or higher surgical complications occurred in 22% of patients in both groups. Furthermore, grade 3 or higher gastrointestinal toxicity occurred in 32% (ECF group) and 30% (chemoradiation group) of patients, while hematologic toxicity occurred in 50 and 52% of patients. CONCLUSIONS: These results demonstrate that preoperative chemoradiation can be safely delivered to the vast majority of patients without a significant increase in treatment toxicity or surgical morbidity.

Phase I trial of radiation therapy and sorafenib in unresectable liver metastases.

BACKGROUND AND PURPOSE: To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases. MATERIAL AND METHODS: Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I - SBRT: effective liver volume irradiated (Veff)<80% (30-60Gy in 6 fractions); II - WLRT: Veff>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2-3, was delivered at 3 escalating dose levels (200-400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity. RESULTS: Thirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively. CONCLUSIONS: Sorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.

Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer.

PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. RESULTS: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. CONCLUSION: Cisplatin can be safely delivered with 5-FU-based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

Changes in Liver Volume Observed Following Sorafenib and Liver Radiation Therapy.

PURPOSE: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). METHODS AND MATERIALS: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT). Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. RESULTS: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). CONCLUSIONS: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.

Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). METHODS AND MATERIALS: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. RESULTS: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. CONCLUSIONS: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.

TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG).

BACKGROUND: The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy. METHODS/DESIGN: Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. DISCUSSION: TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000035224 . Registered 30 May 2009.

Ginseng and anticancer drug combination to improve cancer chemotherapy: a critical review.

Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable.

Edible bird's nest: food or medicine?

Edible bird's nest (EBN) is derived from the saliva of certain types of swiftlets. It is consumed in many parts of the world for its nutritional and medicinal values. Although many claims have been made on the therapeutic and health-promoting effects of EBN, scientific documentations regarding these effects are very limited in published literature. It is not until recently that the biological effects of EBN are being investigated and evidence-based studies are being conducted. Several studies have found that EBN may enhance cell proliferation and differentiation and various beneficial effects have been reported in vitro as well as in vivo. While these studies point towards the potential use of EBN in the treatment or even prevention of several diseases, the mechanisms of action of EBN remain largely unknown and more explorations are needed. This review is one of the very few scientific reviews on EBN which focuses on recent evidence-based discoveries.

A randomized, controlled clinical trial: the effect of mindfulness-based cognitive therapy on generalized anxiety disorder among Chinese community patients: protocol for a randomized trial.

BACKGROUND: Research suggests that an eight-week Mindfulness-Based Cognitive Therapy (MBCT) program may be effective in the treatment of generalized anxiety disorders. Our objective is to compare the clinical effectiveness of the MBCT program with a psycho-education programme and usual care in reducing anxiety symptoms in people suffering from generalized anxiety disorder. METHODS: A three armed randomized, controlled clinical trial including 9-month post-treatment follow-up is proposed. Participants screened positive using the Structure Clinical Interview for DSM-IV (SCID) for general anxiety disorder will be recruited from community-based clinics. 228 participants will be randomly allocated to the MBCT program plus usual care, psycho-education program plus usual care or the usual care group. Validated Chinese version of instruments measuring anxiety and worry symptoms, depression, quality of life and health service utilization will be used. Our primary end point is the change of anxiety and worry score (Beck Anxiety Inventory and Penn State Worry Scale) from baseline to the end of intervention. For primary analyses, treatment outcomes will be assessed by ANCOVA, with change in anxiety score as the baseline variable, while the baseline anxiety score and other baseline characteristics that significantly differ between groups will serve as covariates. CONCLUSIONS: This is a first randomized controlled trial that compare the effectiveness of MBCT with an active control, findings will advance current knowledge in the management of GAD and the way that group intervention can be delivered and inform future research. Unique Trail Number (assigned by Centre for Clinical Trails, Clinical Trials registry, The Chinese University of Hong Kong): CUHK_CCT00267.

Comparing the effectiveness of mindfulness-based stress reduction and multidisciplinary intervention programs for chronic pain: a randomized comparative trial.

OBJECTIVES: Research suggests that an 8-week Mindfulness-Based Stress Reduction (MBSR) program (a structured form of meditation) might be effective in the treatment of various health problems including chronic pain. Our objective was to compare the clinical effectiveness of the MBSR program with a multidisciplinary pain intervention (MPI) program in terms of pain intensity, pain-related distress, quality of life, and mood in patients with chronic pain. METHODS: A randomized, comparative clinical trial was conducted, including 6-month posttreatment follow-up. Ninety-nine participants, aged 24 to 64 years, with pain for a minimum of 3 months, were recruited from community-based clinics, hospitals, and community service centers. Participants were randomly allocated to either the MBSR program (51 participants) or a MPI program (48 participants). The study used validated Chinese versions of self-reported questionnaires measuring pain, mood symptoms, and health-related quality of life. RESULTS: Thirty-nine participants (77%) completed the MBSR program and 44 (90%) completed the MPI program. Patients in both the groups were comparable with regard to demographical characteristics, pain intensity, mood symptoms, and health-related quality-of-life measures before intervention. In both the groups, patients who completed the trial demonstrated statistically significant improvements in pain intensity and pain-related distress. However, no statistically significant differences were observed in overall results between the MBSR and MPI groups. CONCLUSIONS: This randomized, clinical trial showed that both MBSR and MPI programs reduced pain intensity and pain-related distress although no statistically significant differences were observed between the 2 groups and the improvements were small.

Patterns of practice in palliative radiotherapy for painful bone metastases: impact of a regional rapid access clinic on access to care.

PURPOSE: External beam radiotherapy (RT) is commonly indicated for the palliation of symptomatic bone metastases, but there is evidence of underutilization of this treatment modality in palliative care for cancer populations. This study was conducted to investigate factors that influenced the use of palliative RT services at a regional comprehensive cancer center. METHODS AND MATERIALS: A cohort of patients with radiographically confirmed bone metastases and first-time users of palliative RT between 2003 and 2005 was retrospectively reviewed from the time of initial diagnosis of bone metastases to death or last follow-up. Type of radiation treatment service provider used (rapid access or routine access) and patient-, tumor-, and treatment-related factors were analyzed for their influences on the number of treatment courses given over the duration of disease. RESULTS: A total of 887 patients received 1,354 courses of palliative RT for bone metastases at a median interval of 4.0 months between courses. Thirty-three percent of patients required more than one RT course. Increased age and travel distance reduced the likelihood and number of treatment courses, while service through a rapid access clinic was independently associated with an increase in subsequent use of palliative RT. CONCLUSIONS: A rapid access service model for palliative RT facilitated access to RT. Travel distance and other factors remained substantial barriers to use of palliative RT services. The pattern of practice suggests an unmet need for symptom control in patients with bone metastases.

A randomized controlled trial of mental imagery augment generalization of learning in acute poststroke patients.

BACKGROUND AND PURPOSE: Our previous studies demonstrated that mental imagery intervention enhanced poststroke patients relearning daily task performance. This study aimed to test the efficacy of mental imagery for promoting generalization of the task skills learned in a training environment to trained and untrained tasks carried out in a novel environment. METHODS: Thirty-five acute poststroke patients were randomly assigned to the mental imagery (MI; n=18) or conventional functional rehabilitation (FR; n=17) group. The MI intervention was 3-week standardized practices and daily tasks using the chunking-regulation-rehearsal strategies. Outcome measurements were the performances on trained and untrained tasks in the training and novel environments. RESULTS: The MI patients showed significantly better performances on 4 of 5 trained tasks (P=0.001 to 0.026) versus only 1 task in the FR patients (P=0.021). The MI patients also outperformed their FR counterpart on the 3 (of 5) (P=0.025 to 0.049) trained and 2 (of 3) untrained tasks (P=0.042 to 0.045) carried out in the novel environment. CONCLUSIONS: The mental imagery intervention was useful for improving patients' ability on performing the tasks which they did not previously trained on and in places different from the training environments. These involved generalization of the skills learned at the task performance level. Our findings are limited to poststoke patients who share similar characteristics with those in this study.

Online planning and delivery technique for radiotherapy of spinal metastases using cone-beam CT: image quality and system performance.

PURPOSE: To assess the feasibility of an online strategy for palliative radiotherapy (RT) of spinal bone metastasis, which integrates imaging, planning, and treatment delivery in a single step at the treatment unit. The technical challenges of this approach include cone-beam CT (CBCT) image quality for target definition, online planning, and efficient process integration. METHODS AND MATERIALS: An integrated imaging, planning, and delivery system was constructed and tested with phantoms. The magnitude of CBCT image artifacts following the use of an antiscatter grid and a nonlinear scatter correction was quantified using phantom data and images of patients receiving conventional palliative RT of the spine. The efficacy of online planning was then assessed using corrected CBCT images. Testing of the complete process was performed on phantoms with assessment of timing and dosimetric accuracy. RESULTS: The use of image corrections reduced the cupping artifact from 30% to 4.5% on CBCT images of a body phantom and improved the accuracy of CBCT numbers (water: +/- 20 Hounsfield unit [HU], and lung and bone: to within +/- 130 HU). Bony anatomy was clearly visible and was deemed sufficient for target definition. The mean total time (n = 5) for application of the online approach was 23.1 min. Image-guided dose placement was assessed using radiochromic film measurements with good agreement (within 5% of dose difference and 2 mm of distance to agreement). CONCLUSIONS: The technical feasibility of CBCT-guided online planning and delivery for palliative single treatment has been demonstrated. The process was performed in one session equivalent to an initial treatment slot (<30 min) with dosimetric accuracy satisfying accepted RT standards.

Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases.

BACKGROUND: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). METHODS AND MATERIALS: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. RESULTS: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. CONCLUSION: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.