Effect of stress hyperglycemia and intensive rehabilitation therapy in non-diabetic hemorrhagic stroke: Korean Stroke Cohort for Functioning and Rehabilitation.

BACKGROUND AND PURPOSE: We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. METHODS: Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. RESULTS: For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. CONCLUSIONS: Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke.

Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans.

BACKGROUND: The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. METHODS: Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. RESULTS: PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D95%) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower TCP is associated with the lower PTV coverage in AXB-recalculated plans. No obvious trend was observed between the calculation-resulted TCP differences and tumor size or location. AAA and AXB yield very similar NTCP on lung pneumonitis according to the LKB model estimation in the present study. CONCLUSION: AAA apparently overestimates the PTV dose; the magnitude of resulting difference in calculated TCP was up to 5.8 % in our study. AAA and AXB yield very similar NTCP on lung pneumonitis based on the LKB model parameter sets we used in the present study.

Application of Spatially Fractionated Radiation (GRID) to Helical Tomotherapy using a Novel TOMOGRID Template.

Spatially fractionated radiation therapy (GRID) with megavoltage x-ray beam is typically used to treat large and bulky malignant tumors. Currently most of the GRID treatment is performed by using the linear accelerator with either the multileaf collimator or with the commercially available block. A novel method to perform GRID treatments using Helical Tomotherapy (HT) was developed at the Radiation Oncology Department, College of Medicine, the University of Arkansas for Medical Sciences. In this study, we performed a dosimetric comparison of two techniques of GRID therapy: one on linear accelerator with a commercially available GRID block (LINAC-GRID) as planned on the Pinnacle planning station (P-TPS); and helical tomotherapy-based GRID (HT-GRID) technique using a novel virtual TOMOGRID template planned on Tomotherapy treatment planning station (HT-TPS). Three dosimetric parameters: gross target volume (GTV) dose distribution, GTV target dose inhomogeneity, and doses to regions of interest were compared. The comparison results show that HT-GRID dose distributions are comparable to those of LINAC-GRID for GTV coverage. Doses to the majority of organs-at-risk (OAR) are lower in HT-GRID as compared to LINAC-GRID. The maximum dose to the normal tissue is reduced by 120% for HT-GRID as compared to the LINACGRID. This study indicate that HT-GRID can be used to deliver spatially fractionated dose distributions while allowing 3-D optimization of dose to achieve superior sparing of OARs and confinement of high dose to target.

Dosimetric Comparison of Craniospinal Irradiation Using Different Tomotherapy Techniques.

The objective of this study is to compare the new and conventional tomotherapy treatment techniques and to evaluate dosimetric differences between them. A dosimetric analysis was performed by comparing planning target volume (PTV) median dose, 95% of PTV dose coverage, Paddick conformity index (CI), homogeneity index (HI), whole-body integral dose, and OAR median doses. The beam on time (BOT) and the effect of different jaw sizes and pitch values was studied. The study results indicated that the PTV dose coverage for all the techniques was comparable. Treatment plans using dynamic jaw reduced OAR doses to structures located at the treatment field edge compared to fixed jaw plans. The HT-3DCRT plans resulted in higher OAR doses to kidney, liver, and lung compared to the other techniques, and TD-IMRT provided the best dose sparing to liver compared to other techniques. Whole-body integral dose differences were found to be insignificant among the techniques. BOT was found to be higher for fixed jaw treatment plan compared to dynamic jaw plan and comparable between all treatment techniques with 5-cm dynamic jaw. In studying effect of jaw size, better OAR sparing and HI were found for 2.5-cm jaw but at the expense of doubling of BOT as compared to 5-cm jaw. There was no significant improvement found in OAR sparing when the pitch value was increased. Increasing the pitch from 0.2 to 0.43, the CI was improved, HI improved only for 5-cm jaw size, and BOT decreased to approximately half of its original time.

Stability of HER2-positive status in breast carcinoma: a comparison between primary and paired metastatic tumors with regard to the possible impact of intervening trastuzumab treatment.

BACKGROUND: To date, the stability of human epidermal growth factor receptor 2 (HER2)-positive primary breast carcinomas during disease progression and the role of intervening trastuzumab treatment in the loss of HER2-positive status in paired metastases remain under-investigated. MATERIALS AND METHODS: Sixty-six patients with HER2-positive primary carcinoma and paired metastasis were evaluated. We examined the overall agreement of the HER2 status and compared the status agreement between 38 trastuzumab-treated patients and 28 trastuzumab-naive control patients. The impact of chemotherapy, endocrine therapy, metastatic site (locoregional or distant), and time to relapse (≥5 or <5 years) on the HER2 status change was assessed. RESULTS: Fifty-six (84.9%) patients had HER2 status agreement between paired tumors; 10 patients had HER2-positive-to-negative conversion. The agreement rate in the trastuzumab-treated group and in the control group was comparable (86.8% versus 82.1%) (P = 0.858). Chemotherapy, endocrine therapy, metastatic site, and time to relapse did not significantly affect HER2 stability in either group. In the discordant tumor pairs, variations in testing methods and borderline scores were common. CONCLUSIONS: HER2-positive status remained unchanged in most paired metastases. Loss of HER2-positive status did not seem to be affected by trastuzumab treatment. Differences in testing and interpretation may account for the discordance in some cases.

Evaluation of surface and superficial dose for head and neck treatments using conventional or intensity-modulated techniques.

With increased use of intensity-modulated radiation therapy (IMRT) for head and neck treatment questions have arisen as to selection of an optimum treatment approach when either superficial sparing or treatment is desired. Other work has pointed out the increased superficial dose resulting from obliquity effects when multiple tangential beams are applied to head and neck treatment, as is the general case in IMRT planning. Helical tomotherapy might be expected to result in even further enhanced superficial dose compared with conventional bilateral field treatment. We have designed a typical right oropharynx target volume in an anthropomorphic head and neck phantom. Three different treatment techniques have been used to optimally treat this target, including bilateral static fields, eight-field IMRT and helical tomotherapy. The phantom was immobilized in a standard treatment position and treated on a Varian 2300cd linear accelerator and on a Hi-Art Helical Tomotherapy unit. 1 mm3 lithium-fluoride thermoluminescent dosimeters (TLDs) were placed on the surface of the phantom at a number of axial test positions. Film strips (Kodak EDR2) were either wrapped around the surface or sandwiched within the phantom. Measured doses at the surface and as a function of depth are compared with the planning system predictions for each treatment technique. The maximum surface doses on the proximal treatment side, averaged from TLDs and films, were measured to be 69-82% of the target dose with the bilateral fields yielding the lowest surface doses (69%), tomotherapy about 2% more than that (71%) and IMRT 13% more (82%). Anterior to the target volume, doses are always low for bilateral treatment. In this case the minimum anterior surface dose (chin area) was 6% of the prescription dose from that technique as compared with 26% and 35% from the IMRT and tomotherapy methods, respectively. The Eclipse and Tomotherapy planning systems both modelled deep and superficial doses well. Surface doses were better modelled by Eclipse at the test points, while the tomotherapy plans consistently overestimated the measured doses by 10% or more. Depth dose measurements, extracted from embedded films, indicated the depth of dose build-up to >99% to be the shallowest for IMRT (2-5 mm) followed by tomotherapy (5-8 mm) and bilateral fields (10-15 mm). The amount of surface dose is clearly technique dependent and should be taken into account in the planning stage.

Effects of 20-week intermittent cold-water-immersion on phenotype and myonuclei in single fibers of rat hindlimb muscles.

The effects of 20 weeks of intermittent cold-water-immersion on myosin heavy chain (MHC) expression,cross-sectional area (CSA), myonuclear number, and myonuclear domain size in isolated single fiber of soleus and extensor digitorum longus (EDL) muscles were studied in male Wistar rats. Cold exposure was accomplished by submerging the rats in shoulder-deep water, maintained at approximately 18 degrees C, for 1 hour/day, 5 days/week and for 20 weeks. Cold exposure resulted in a significant inhibition of body and soleus muscle weight gain. The percent type IIa MHC fibers of EDL muscle was increased, whereas that of type IIa + b MHC fibers was less in cold-exposed group than controls (p < 0.05). The mean CSA and myonuclear number in type I MHC fibers of soleus muscle in cold-exposed group were significantly less than controls. Myonuclear domain in type IIa fibers of EDL in the cold-exposed group was greater than controls (p < 0.05). It is suggested that prolonged cold exposure causes the fiber-type-specific adaptation in rat hindlimb muscles. It is further indicated that cold-exposure-related modulation of myonuclear number was closely related to reduction of fiber CSA, not the shift of fiber phenotype.

Effects of 9 weeks of hindlimb unloading on motor performances in adult rats.

It has been reported that abnormal steps associated with an ankle hyper-extension during walking were observed in adult rats after 2 weeks of hindlimb suspension (Canu and Falempin, 1997 & 1998). But such phenomena were normalized after 7 days of reambulation recovery. Canu and Falempin (1996) suggested that the spinal cord has a capacity to generate a well-organized pattern of locomotion even after a period of muscle disuse. There are, however, no reports about the effects of more prolonged suspension on motor performances. In the present study, 7 weeks old male rats were hindlimb-unloaded by tail suspension for 9 consecutive weeks and landing performances in response to drop from head-down, head-up, or supine position were investigated during 8 weeks of recovery. Posture maintenance during right-left translation was also checked.