Clinical examination of proton pencil beam scanning on a moving anthropomorphic lung phantom.

The objective of this study was to examine the use of proton pencil beam scanning for the treatment of moving lung tumors. A single-field uniform dose proton pencil beam scanning (PBS) plan was generated for the standard thorax phantom designed by the Imaging and Radiation Oncology Core (IROC) Houston QA Center. Robust optimization, including range and setup uncertainties as well as volumetric repainting, was used for the plan. Patient-specific quality assurance (QA) measurements were performed using both a water tank and a custom heterogeneous QA phantom. A custom moving phantom was used to find the optimal number of volumetric repainting. Both analytical and Monte Carlo (MC) algorithms were used for dose calculation and their accuracies were compared with actual measurements. A single ionization chamber, a 2-dimensional ionization chamber array, thermoluminescent dosimeters (TLDs), and films were used for dose measurements. The optimal number of volumetric repainting was found to be 4 times in our system. The mean dose overestimations on a moving target by analytical and MC algorithms based on a time-averaged computed tomography (CT) image of the phantom were found to be 4.8% and 2.4%, respectively. The mean gamma indexes for analytical and MC algorithms were 91% and 96%, respectively. The MC dose algorithm calculation was found to have a better agreement with measurements compared with the analytical algorithm. When treating moving lung tumors using proton PBS, the techniques of robust optimization, volumetric repainting, and MC dose calculation were found effective. Extra care needs to be taken when an analytical dose calculation algorithm is used.

Hemostatic and inflammatory risk factors for intracerebral hemorrhage in a pooled cohort.

BACKGROUND AND PURPOSE: The purpose of this study was to identify novel risk factors for intracerebral hemorrhagic stroke (ICH). METHODS: Risk factors were assessed at baseline in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) involving 21,680 adults aged 45 or over. Over 263,489 person-years of follow-up, we identified 135 incident ICH events. RESULTS: In multivariable models, for each SD higher baseline level of fibrinogen, the relative rate of incident ICH increased 35% (95% CI, 17% to 55%). Fibrinogen was more strongly related to ICH in ARIC than in CHS. In multivariable models, those with von Willebrand factor levels above the median were 1.72 (95% CI, 0.97 to 3.03) times more likely to have an incident ICH as those below the median. Factor VIII was significantly positively related to ICH in ARIC (relative rate per standard deviation of 1.31; 95% CI, 1.07 to 1.62), but not in CHS. There was no relation in multivariable models between lipoprotein (a), Factor VII, white blood cell count, or C-reactive protein and ICH. CONCLUSIONS: Greater plasma fibrinogen and, to some degree, von Willebrand factor were associated with increased rates of ICH in these prospective studies, whereas Factor VIII was related to ICH in younger ARIC study participants only.

Four-dimensional Plan Optimization for the Treatment of Lung Tumors Using Pencil-beam Scanning Proton Radiotherapy.

Purpose  This study aimed to evaluate the effectiveness of four-dimensional (4D) robust optimization for proton pencil-beam scanning (PBS) treatment of lung tumors. Patients and methods  In seven patients with lung cancer, proton beam therapy was planned using 4D robust optimization over 4D computed tomography (CT) data sets. The gross target volume (GTV) was contoured based on individual breathing phases, and a 5-mm expansion was used to generate the clinical target volume (CTV) for each phase. The 4D optimization was conducted directly on the 4D CT data set. The robust optimization settings included a CT Hounsfield unit (HU) uncertainty of 4% and a setup uncertainty of 5 mm to obtain the CTV. Additional target dose objectives such as those for the internal target volume (ITV) as well as the organ-at-risk (OAR) dose requirements were placed on the average CT. For comparison, three-dimensional (3D) robust optimization was also performed on the average CT. An additional verification 4D CT was performed to verify plan robustness against inter-fractional variations. Results  Target coverages were generally higher for 4D optimized plans. The difference was most pronounced for ITV V70Gy when evaluating individual breathing phases. The 4D optimized plans were shown to be able to maintain the ITV coverage at full prescription, while 3D optimized plans could not. More importantly, this difference in ITV V70Gy between the 4D and 3D optimized plans was also consistently observed when evaluating the verification 4D CT, indicating that the 4D optimized plans were more robust against inter-fractional variations. Less difference was seen between the 4D and 3D optimized plans in the lungs criteria: V5Gy and V20Gy. Conclusion  The proton PBS treatment plans optimized directly on the 4D CT were shown to be more robust when compared to those optimized on a regular 3D CT. Robust 4D optimization can improve the target coverage for the proton PBS lung treatments.

Risk factors for intracerebral hemorrhage in a pooled prospective study.

BACKGROUND AND PURPOSE: Few prospective studies have reported risk factors for intracerebral hemorrhage (ICH), and results are inconsistent. We studied risk factors for ICH in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). METHODS: The ARIC cohort was recruited in 1987 to 1989 and involves 15 792 men and women, aged 45 to 64 years at baseline, sampled from 4 US communities. The CHS cohort was recruited in 1989 to 1993 and involves 5888 men and women, aged 65 or over at baseline, sampled from 4 US communities. Baseline measurements included many potential vascular risk factors. The cohorts were followed for incident stroke events. RESULTS: Over 263 489 person-years of follow-up, 135 incident ICH events occurred. In a multivariable model, age, African-American ethnicity (versus Whites), and hypertension were positively associated with incident ICH, whereas low-density lipoprotein cholesterol and triglycerides were inversely related to incident ICH. Participants with systolic blood pressure >or=160 mm Hg or diastolic blood pressure >/=110 mm Hg had 5.55 (95% CI 3.07 to 10.0) times the rate of ICH as nonhypertensives. Sex, smoking, alcohol intake, body mass index, waist-to-hip ratio, waist circumference, and diabetes were not related to ICH. CONCLUSIONS: In this pooled cohort the risk factors for ICH were older age, African-American ethnicity, hypertension, lower LDL-C, and lower triglycerides.

Robust Planning for a Patient Treated in Decubitus Position with Proton Pencil Beam Scanning Radiotherapy.

A challenging case was reported for a patient treated in decubitus position with proton pencil beam scanning. A regular robust plan with the consideration of the uncertainties of translational alignment and range accuracy cannot ensure the target coverage as revealed in two verification computed tomography (CT) scans during the first week of the treatment. The irreproducibility of daily alignment and anatomical variations in such a position is mainly due to patient's roll. To mitigate the interfractional effect on the target coverage, a novel robust optimization against the patient's angular setup uncertainties was implemented to improve the plan quality by introducing two artificial CT image sets by rolling the planning CT three degrees in both clockwise and counter-clockwise directions and adding them into robust optimization scenarios, which was shown to be an effective and simple way to mitigate target dose degradation with respect to interfractional variations. This method can be easily generalized and applied to other situations where angular variations in patient's setup can introduce large dosimetric effects. It is recommended that angularly robust optimization method should be integrated into the treatment planning system as an option particularly for patient's treatment subject to large angular variations, such as the one in the decubitus position reported here.

Definitive Chemoradiation for Squamous Cell Carcinoma of the Rectum.

OBJECTIVES: Squamous cell carcinoma (SCC) of the rectum is a rare disease with <80 cases reported in the English literature. We reviewed outcomes in patients with SCC of the rectum treated with definitive chemoradiation at a single institution. MATERIALS AND METHODS: We identified 14 patients treated definitively with chemoradiation for SCC of the rectum. All patients were female and the median age was 56 years at presentation. Patients were treated with external beam radiation therapy with a median dose of 54 Gy (range, 38 to 58.8 Gy). All patients received concurrent chemotherapy, with 5-flourouracil and cisplatin in 10 patients and capecitabine and cisplatin in 4 patients. RESULTS: The median follow-up was 4.5 years (range, 1.8 to 16.3 y). Only 3 of the 14 patients had relapse or persistent disease, and 2 of these underwent successful salvage surgery. The remaining 11 patients had no evidence for local or distant relapse after chemoradiation. Only 1 patient died of SCC of the rectum, 1 died of a second primary, and 12 are alive with no evidence of disease. The 5-year actuarial overall survival, disease-free survival, and disease-specific survival rates were 81%, 72%, and 88% respectively. CONCLUSIONS: Chemoradiation is an ideal strategy for definitive therapy of SCC of the rectum with excellent disease-free survival and overall survival. In patients with local failure, salvage surgery can provide excellent outcomes.

Apolipoprotein E genotype and incident ischemic stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: A relationship between the apolipoprotein E (apoE) genotype and ischemic stroke has been inconsistently reported. We explored this relation in the Atherosclerosis Risk in Communities Study (ARIC). METHODS: The ARIC cohort involves 15 792 men and women, aged 45 to 64 years at baseline and sampled from 4 U.S. communities. Between 1987 and 2001, 498 incident ischemic strokes occurred. RESULTS: After stratifying by race and sex and adjusting for other nonlipid risk factors, there was no significant relation between the apoE genotype and incident stroke, except in black women (hazard ratio for epsilon2 genotype relative to epsilon3/epsilon3=0.53; 95% CI, 0.28 to 0.99). CONCLUSIONS: For the most part, in this middle-aged sample, apoE was not a risk factor for incident ischemic stroke.

Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

PURPOSE: Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. METHODS: Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0-5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman's test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. RESULTS: The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error ([Formula: see text]) and for [Formula: see text]-axis [Formula: see text]. Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to [Formula: see text]2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. CONCLUSIONS: Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs [Formula: see text]2 mm should be utilized for DRR generation in the head and neck.

Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah.

BACKGROUND: This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. METHODS: Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. RESULTS: LDS men had a 31% (95% confidence interval, 26%-36%) higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985-88, 20% in 1989-92, 15% in 1993-1996, and 13% in 1997-99); age (13% in ages 50-59, 48% in ages 60-69, 28% in ages 70-79, and 16% in ages 80 and older); and stage (36% in local/regional and 17% in unstaged). An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. CONCLUSIONS: Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

Trends in hospitalization rate, hospital case fatality, and mortality rate of stroke by subtype in Minneapolis-St. Paul, 1980-2002.

BACKGROUND: The stroke mortality rates have been declining in the USA for decades. Less is known about trends in stroke incidence rates, but some studies indicate they have declined. The stroke case fatality has also been declining. Little information exists on trends in stroke subtypes. We examined trends in mortality, hospitalization rate, and hospital case fatality of stroke by subtype in the Minneapolis-St. Paul area from 1980 to 2002. METHODS: We estimated hospitalization rates and case fatality for > or =30-year-olds with data from the Minnesota Hospital Association. We estimated mortality rates with counts from the Minnesota Department of Health. Rates were age adjusted to the US 2000 standard by the direct method using census estimates. We tested for significant trends using linear regression. RESULTS: Total stroke mortality and hospital case fatality both declined by almost 50% over the study period, while the rate of stroke hospitalization was relatively stable. Ischemic stroke hospitalization rates increased, while hospital case fatality and mortality rates decreased. Subarachnoid hemorrhage in-hospital case fatality and mortality rates declined, while the hospitalization rate was stable. Intracerebral hemorrhage hospitalization rates increased minimally, hospital case fatality declined, and the mortality rate was stable. CONCLUSION: These data suggest that declines in total stroke case fatality are contributing most to declining mortality rates in the presence of stable total stroke attack rates.