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Acceptance of traditional chinese medicine (TCM) treatment is important in cancer patients to improve treatment efficacy, reduce side effects and prolong prognosis and survival rate. However, such studies and validated instruments that assess the acceptance of TCM treatment in Malaysia are limited. This study aimed to evaluate the validity and reliability of the acceptance of the TCM treatment questionnaire based on applying the Theory of Planned Behaviour. The validation study was conducted in two phases. The first phase included content validation, adaptation and face validity using the Survey Validation Rubric for Expert Panel (VREP). The second phase included construct reliability by using Cronbach alpha. The first phase validation of the questionnaire met expectations from the experts' panel with a score of 3.33. In phase two, 78 patients were included in the analysis. All constructs achieved a Cronbach Alpha >0.8, showing good reliability of the questionnaire. This study demonstrated good validity and reliability of the major constructs in the acceptance of the TCM questionnaire. Our results showed that the acceptance of the TCM questionnaire was a reliable instrument that could be applied to evaluate the acceptance of TCM treatment among cancer patients. [ABSTRACT FROM AUTHOR]

Linked Articles: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc. [ABSTRACT FROM AUTHOR]

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This study investigated the effect of human parathyroid hormone replacement therapy on specific disease-related outcomes in patients with hypoparathyroidism. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until January 13, 2015 for randomized trials using the following search terms: hypoparathyroidism, parathyroid hormone/PTH, and hormone replacement therapy. Five randomized controlled trials (n = 245) that investigated effect of either PTH (1-34) (3 trials) or PTH (1-84) (2 trials) on serum calcium, phosphate, 1,25-dihydroxy-vitamin D, 25-dihydroxyvitamin D levels, and urine level of calcium were included in the meta-analysis. Both PTH (1-34) and PTH (1-84) therapies were not associated with change in serum calcium level compared with calcitriol/placebo. The level of 24-h urine calcium excretion had a significant decrease in PTH (1-34)-treated group compared placebo/ calcitriol (control) group (p≤0.012). PTH (1-34) did not change serum phosphate (p = 0.053). PTH ( 1 -84) did not change level of 24-h urine calcium excretion compared with control (p≥0.214) but it did decrease the levels of serum phosphorous (p = 0.000). Both PTH-replacement therapies were not associated with change in serum 1,25-dihydroxyvitamin D level compared with control (p≥0.606), but were associated with a significant decrease in serum 25-dihydroxyvitamin D levels (p≤0.04). In conclusion, although the number of randomized trial is limited, our meta-analysis suggests that PTH (1-34) replacement therapy may maintain the serum calcium levels in the normal range by reducing the levels of urine calcium excretion, and both replacement therapies may maintain 1,25-dihydroxyvitamin D serum levels by reducing serum level of 25-dihydroxyvitamin D. [ABSTRACT FROM AUTHOR]

Background The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACC's propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum-based chemotherapy. Methods Nine patients with unresectable node-negative, nonmetastatic head and neck ACC received definitive proton RT and concurrent cisplatin. Outcomes and toxicities were recorded. A systematic review of the literature was performed. Results Median follow-up was 27 months (range, 9.2-48.3 months). Four patients achieved complete response at the primary site, and an additional 4 patients achieved stabilization of local disease. Only 1 patient developed local disease progression. Four patients had 5 acute grade 3 (G3) toxicities, and 1 patient developed a chronic G4 optic nerve disorder. Conclusion Our preliminary results suggest proton RT and concurrent chemotherapy is a definitive treatment option for select patients with head and neck ACC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1472-E1480, 2016 [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the effect of low-dose adenosine on hepatic artery flow (HAF) when administered intraoperatively by continuous infusion. Materials and Methods Between January 2009 and August 2009, 74 patients underwent orthotopic liver transplantation (OLT). Ten patients were enrolled for adenosine treatment, and 64 non-study patients served as controls. After arterial reperfusion, a 16-G central venous catheter was placed in the gastroduodenal artery, and adenosine was continuously infused at doses ranging from 0.7 to 2.8 μg/kg/min for 30 min. HAF and portal vein flow were measured using a transit time flow meter before adenosine infusion, during infusion, and 10 min after infusion. Liver function tests were monitored routinely, duplex ultrasonography was performed on postoperative day 1, and the hepatic artery resistive index measured. The patients were followed for 1 year. Results Adenosine significantly increased HAF at doses from 0.7 to 2.8 μg/kg/min. The smallest increase in HAF was 24% above the baseline; in 80% of patients, the increase in HAF was >50% of the baseline values. In 2 patients, HAF was increased by >300%. The dosing started at 0.7 μg/kg/min, and 6 of 10 patients responded. Three patients required an increase to 1.4 μg/kg/min. Doses >2.8 μg/kg/min did not further increase HAF. One patient showed a minimal response regardless of the dose. There were no differences between the adenosine group and control group with respect to liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and International Normalized Ratio), platelet count on POD2, hepatic artery resistive index, and post-transplant length of stay, intensive care days, or 1-year patient survival rates. Conclusions This pilot study established that adenosine administered directly into the hepatic artery produces a similar effect on HAF in cadaveric liver transplant recipients to that found in the laboratory without producing systemic side effects. [ABSTRACT FROM AUTHOR]

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 108 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells. [ABSTRACT FROM AUTHOR]

Echinocandins and triazoles were proven to be effective antifungal drugs against invasive fungal infections (IFI), which may cause significant morbidity and mortality in immunocompromised patients. The aim of this study was to compare the efficacy and safety between echinocandins and triazoles for the prophylaxis and treatment of fungal infections. PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) up to July 2014. The quality of trials was assessed with the Jadad scoring system. The primary outcomes of interest were treatment success, microbiological success, breakthrough infection, drug-related adverse events (AEs), withdrawals due to AEs, and all-cause mortality. Ten RCTs, involving 2,837 patients, were included, as follows: caspofungin versus fluconazole ( n = 1), caspofungin versus itraconazole ( n = 1), anidulafungin versus fluconazole ( n = 1), micafungin versus fluconazole ( n = 4), micafungin versus voriconazole ( n = 2), and micafungin versus itraconazole ( n = 1). Echinocandins and triazoles showed similar effects in terms of favorable treatment success rate [relative risk (RR) = 1.02, 95 % confidence interval (CI), 0.97-1.08], microbiological success rate (RR = 0.98, 95 % CI, 0.90-1.15), breakthrough infection (RR = 1.09; 95 % CI, 0.59-2.01), drug-related AEs (RR = 0.94; 95 % CI, 0.71-1.15), and all-cause mortality (RR = 0.85; 95 % CI, 0.66-1.10) in the prophylaxis and treatment of fungal infections. Additionally, echinocandins were more effective than triazoles for prophylaxis in patients undergoing hematologic malignancies or those who received hematopoietic stem cell transplantation (HSCT; RR = 1.08; 95 % CI, 1.02-1.15). Echinocandins significantly decreased the AE-related withdrawals rate compared with triazoles (RR = 0.47; 95 % CI, 0.33-0.67). This meta-analysis revealed that echinocandins are as effective and safe as triazoles for the prophylaxis and treatment of patients with fungal infections. [ABSTRACT FROM AUTHOR]

Primary graft failure (pGF) is a frequent complication following cord blood transplantation (CBT). For those patients who will not experience autologous recovery, salvage transplantation should be performed as early as possible. However, standardized treatment protocols for pGF, such as the optimal stem cell source, preparative regimen and the ideal time for salvage transplantation, have yet to be determined. Therefore, we analyzed 17 hematologic malignancy patients who received unmanipulated haploidentical peripheral blood (PB) and BM transplantation with reduced-intensity conditioning (RIC) as a salvage therapy for pGF after CBT. The median interval between the two transplantations was 38 days. The RIC regimen for salvage transplantation consisted of fludarabine, antithymocyte globulin, CY and low-dose TBI. The neutrophil and plt engraftments were achieved in 14 (82.4%) and 13 (76.4%) patients, respectively. The cumulative incidences of grades II-IV and grades III-IV aGVHD were 35.3% and 17.6%, respectively. The cumulative incidence of chronic GVHD was 29.4%. After a median follow-up of 43 months, 10 of 17 patients remained alive in CR. The cumulative incidence of TRM at 180 days was 29.4%. The probability of 3-year OS and leukemia-free survival was 57.5%. Our results show that unmanipulated haploidentical PB and BM transplantation under a RIC regimen is an effective treatment for pGF after CBT. [ABSTRACT FROM AUTHOR]

Purpose To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable. [ABSTRACT FROM AUTHOR]

HIV-1 latency remains the primary obstacle to the eradication of this virus. The current latency-reversing agents cannot effectively and specifically eliminate latent HIV-1 reservoirs. Therefore, better approaches are urgently needed. In this study, we describe a novel strategy to reactivate latent HIV-1 using zinc-finger transcription factors composed of designer zinc-finger proteins and the transcriptional activation domain VP64. For the first time, we demonstrate that ZF-VP64 with HIV-1 long terminal repeat (LTR) promoter-specific affinity could significantly reactivate HIV-1 expression from latently infected cells without altering cell proliferation or cell cycle progression. We also provide evidence that the reactivation of HIV-1 by ZF-VP64 occurs through specific binding to the 5′-LTR promoter. Our results demonstrate the potential of this novel approach for anti-HIV-1 latency therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 ± 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyperuricemia and posttransplantation erythrocytosis (PTE) are frequent complications after kidney transplantation and are important risk factors for cardiovascular events. Losartan decreases serum uric acid and hemoglobin (Hb) concentrations and may be a useful agent for treatment of hyperuricemia and PTE. Objective: To evaluate the influence of losartan on serum creatinine (SCr), serum uric acid, and hemoglobin (Hb) concentrations in patients after kidney transplantation and to evaluate the safety profile of losartan in these patients. Patients and Methods: Sixty-six Han Chinese patients (43 men and 23 women; mean [SD] age, 40.45 [11.50] years) were enrolled in the study. All patients had undergone a first cadaveric donor kidney transplantation at least 3 months previously and had stable graft function with SCr concentration less than 176.8 μmol/L and Hb concentration greater than 110 g/L. The patients were divided into 2 groups (losartan group, n = 34; and control group, n = 32) according to the odevity of patient identification number. Patients in the losartan group received losartan, 50 mg/d; patients in the control group did not receive losartan. Each patient was followed up for 6 months. Results: Nine patients in the losartan group and 5 patients in the control group dropped out because of acute renal insufficiency, anemia, acute rejection, or poor compliance. The serum uric acid concentration in the losartan group continuously decreased at months 1, 2, 3, and 6 (P = .12, P = .01, P = .04, and P = .005 compared with baseline, and P = .02, P = .003, P = .02, and P = .006 compared with control), especially in the patients with hyperuricemia (P = .02, P < .001, P = .003, and P < .001 compared with baseline, and P = .02, P = .002, P = .02, and P = .002 compared with control). The Hb level in the losartan group decreased significantly at months 1, 2, 3, and 6 (P = .003, P < .001, P = .004, and P = 0.02 compared with baseline, and P = .001, P < .001, P = .001, and P = .005 compared with control), especially in patients with PTE. In patients without PTE, there was no significant decline in Hb concentration in the losartan group compared with baseline. There was no significant decline in estimated glomerular filtration rate in the losartan group. Conclusions: Losartan may be an effective agent for treatment of hyperuricemia and PTE in Han Chinese patients after kidney transplantation. However, in some patients, losartan may not be safe. [Copyright &y& Elsevier]

A hallmark of cell-surface processes involving glycans is their multivalent interaction with glycan binding proteins (GBPs). Such a multivalent interaction depends critically on the mobility and density of signaling molecules on the membrane surface. While glycan microarrays have been used in exploring multivalent interactions, the lack of mobility and the difficulty in controlling surface density both limit their quantitative applications. Here we apply a fluidic glycan microarray, with glycan density varying for orders of magnitude, to profile cell surface interaction using a model system, the adhesion of Escherichia coli to mannose. We show the quantitative determination of monovalent and multivalent adhesion channels; the latter can be inhibited by nanopartices presenting a high density of mannosyl groups. These results reveal a new E. coli adhesion mechanism: the switching in the FimH adhesion protein avidity from monovalent to multivalent as the density of mobile mannosyl groups increases; such avidity switching enhances binding affinity and triggers multiple fimbriae anchoring. Affinity enhancement toward FimH has only been observed before for oligo-mannose due to the turn on of secondary interactions outside the mannose binding pocket. We suggest that the new mechanism revealed by the fluidic microarray is of general significance to cell surface interactions: the dynamic clustering of simple sugar groups (homogeneous or heterogeneous) on the fluidic membrane surface may simulate the functions of complex glycan molecules. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 19-year-old Chinese woman having one-year history of painful papular lesions and later diagnosed to have primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. The patient's skin lesions have partially resolved after receiving four cycles of chemotherapy, which consists of cyclophosphamide, bleomycin and vincristine. However, the patient develops respiratory insufficiency and died from respiratory failure.

Purpose: The objective of this study was to quantify respiratory motion-induced dose uncertainty at the planning stage for step-and-shoot intensity-modulated radiation therapy (IMRT) using an analytical technique. Methods: Ten patients with stage II/III lung cancer who had undergone a planning four-dimensional (4D) computed tomographic scan and step-and-shoot IMRT planning were selected with a mix of motion and tumor size for this retrospective study. A step-and-shoot IMRT plan was generated for each patient. The maximum and minimum doses with respiratory motion were calculated for each plan, and the mean deviation from the 4D dose was calculated, taking delivery time, fractionation, and patient breathing cycle into consideration. Results: For all patients evaluated in this study, the mean deviation from the 4D dose in the planning target volume (PTV) was <2.5%, with a standard deviation <1.2%, and maximum point dose variation from the 4D dose was <6.2% in the PTV assuming delivery dose rate of 200 MU/min and patient breathing cycle of 8 s. The motion-induced dose uncertainty is a function of motion, fractionation, MU (plan modulation), dose rate, and patient breathing cycle. Conclusions: Respiratory motion-induced dose uncertainty varies from patient to patient. Therefore, it is important to evaluate the dose uncertainty on a patient-specific basis, which could be useful for plan evaluation and treatment strategy determination for selected patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to validate the use of HPlusQA, spot-scanning proton therapy (SSPT) dose calculation software developed at The University of Texas MD Anderson Cancer Center, as second-check dose calculation software for patient-specific quality assurance (PSQA). The authors also showed how HPlusQA can be used within the current PSQA framework. Methods: The authors compared the dose calculations of HPlusQA and the Eclipse treatment planning system with 106 planar dose measurements made as part of PSQA. To determine the relative performance and the degree of correlation between HPlusQA and Eclipse, the authors compared calculated with measured point doses. Then, to determine how well HPlusQA can predict when the comparisons between Eclipse calculations and the measured dose will exceed tolerance levels, the authors compared gamma index scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse. The authors introduce the αβγ transformation as a way to more easily compare gamma scores. Results: The authors compared measured and calculated dose planes using the relative depth, z/R × 100%, where z is the depth of the measurement and R is the proton beam range. For relative depths than less than 80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements on average. When the relative depth was greater than 80%, the agreement between the calculations and measurements fell to 4 cGy. For relative depths less than 10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, -0.21. Otherwise, the correlation between the dose discrepancies was positive and as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted when Eclipse had and had not calculated the dose to within tolerance 92% and 79% of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the comparison between measurement and Eclipse's calculation had exceeded the tolerance levels of 3% for dose and 3 mm for distance-to-agreement. Conclusions: The authors found HPlusQA to be reasonably effective (79% ± 10%) in determining when the comparison between measured dose planes and the dose planes calculated by the Eclipse treatment planning system had exceeded the acceptable tolerance levels. When used as described in this study, HPlusQA can reduce the need for patient specific quality assurance measurements by 64%. The authors believe that the use of HPlusQA as a dose calculation second check can increase the efficiency and effectiveness of the QA process. [ABSTRACT FROM AUTHOR]

Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm2/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. Conclusions: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work was to assess the monitor unit (MU) values and position accuracy of spot scanning proton beams as recorded by the daily treatment logs of the treatment control system, and furthermore establish the feasibility of using the delivered spot positions and MU values to calculate and evaluate delivered doses to patients. Methods: To validate the accuracy of the recorded spot positions, the authors generated and executed a test treatment plan containing nine spot positions, to which the authors delivered ten MU each. The spot positions were measured with radiographic films and Matrixx 2D ion-chambers array placed at the isocenter plane and compared for displacements from the planned and recorded positions. Treatment logs for 14 patients were then used to determine the spot MU values and position accuracy of the scanning proton beam delivery system. Univariate analysis was used to detect any systematic error or large variation between patients, treatment dates, proton energies, gantry angles, and planned spot positions. The recorded patient spot positions and MU values were then used to replace the spot positions and MU values in the plan, and the treatment planning system was used to calculate the delivered doses to patients. The results were compared with the treatment plan. Results: Within a treatment session, spot positions were reproducible within ±0.2 mm. The spot positions measured by film agreed with the planned positions within ±1 mm and with the recorded positions within ±0.5 mm. The maximum day-to-day variation for any given spot position was within ±1 mm. For all 14 patients, with ∼1 500 000 spots recorded, the total MU accuracy was within 0.1% of the planned MU values, the mean (x, y) spot displacement from the planned value was (-0.03 mm, -0.01 mm), the maximum (x, y) displacement was (1.68 mm, 2.27 mm), and the (x, y) standard deviation was (0.26 mm, 0.42 mm). The maximum dose difference between calculated dose to the patient based on the plan and recorded data was within 2%. Conclusions: The authors have shown that the treatment log file in a spot scanning proton beam delivery system is precise enough to serve as a quality assurance tool to monitor variation in spot position and MU value, as well as the delivered dose uncertainty from the treatment delivery system. The analysis tool developed here could be useful for assessing spot position uncertainty and thus dose uncertainty for any patient receiving spot scanning proton beam therapy. [ABSTRACT FROM AUTHOR]

Highlight: [•] Cancer chemotherapy-induced fatigue is associated with suppressed hypothalamic orexin neuron activity and orexin administration reverses this fatigue. [Copyright &y& Elsevier]

• Intensity modulated proton therapy is a highly conformal treatment option. • Treatment of inoperable NSCLC with IMPT offers excellent disease local control. • Treatment was well tolerated with no grade 4 or 5 toxicity. We report disease control, survival, and toxicity in patients with advanced inoperable non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy and intensity-modulated proton therapy (IMPT) at a single institution. All patients were treated with IMPT with concurrent chemotherapy. Endpoints assessed were local, regional, and distant control, disease-free survival (DFS), and overall survival (OS). Fifty-one patients were enrolled with a median follow-up time of 23.0 months; 39 (76%) were treated with a simultaneous integrated boost to the gross tumor volume (GTV). The median GTV dose was 67.3 CGE and the median CTV dose was 60.0 CGE. Median OS and DFS times were 33.9 months and 12.6 months. The 3-year local control rate was 78.3%. Treatment was well tolerated, with a grade 3 toxicity rate of 18% (9 events: 4 esophagitis, 3 dermatitis, 1 esophageal stricture, and 1 fatigue) and no grade 4 or 5 toxicity. The most common grade 2 toxic effects were esophagitis (22 [43%]), dermatitis (16 [31%]), pain (15 [29%]), and fatigue (14 [27%]). Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity. [ABSTRACT FROM AUTHOR]

Background: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD.Methods: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 μg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24.Results: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups.Conclusions: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .). [ABSTRACT FROM AUTHOR]