Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.     

Dosimetric study of a respiratory gating technique based on four-dimensional computed tomography in non-small-cell lung cancer

This study sought to compare the differences in target volumes and dose distributions to the targets and organs at risk (OARs) between a four-dimensional computed tomography (4DCT)-based respiratory-gated intensity-modulated radiation therapy (IMRT) plan (Plan_EOE) and a three-dimensional CT (3DCT)-based IMRT plan (Plan_3D) in patients with non-small-cell lung cancer (NSCLC). For 17 patients with Stages I–III NSCLC, both 4DCT data and conventional 3DCT data were obtained. The Plan_3D and Plan_EOE were designed based on 3DCT data and 4DCT data, respectively. The displacements of the gross tumor volume (GTV) centroid were 0.13 ± 0.09 cm, 0.15 ± 0.1 cm, and 0.27 ± 0.27 cm in the right–left, anterior–posterior, and superior–inferior directions, respectively. The volume of the GTV_EOE was 3.05 ± 5.17 cm³ larger than that of the GTV_3D. The volume of the PTV_3D was 72.82 ± 48.65 cm³ larger than that of the PTV_EOE. There was no significant difference between the PTV_3D and PTV_EOE for V55.8, V60, V66 and the homogeneity index. The PTV_3D had a lower target conformity index than the PTV_EOE (P = 0.036). Plan_EOE had a significantly lower lung V10, V20, V30, V40 and mean lung dose (MLD) than Plan_3D. For the heart, Plan_EOE had a significantly lower V₃₀ and mean dose. In conclusion, 4DCT is an appropriate method for assessing the displacement of the GTV centroid in three dimensions. Plan_EOE has smaller PTVs and a decreased dose and volume for the normal lung and heart, as compared with Plan_3D.     

Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume

We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. − (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose–volumetric analysis, the trial regimen of 60 Gy/5 fr. − (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. − (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0–27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. − (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. − (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. − (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity.     

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0–1 RP (RP_G≤1) group and the Grade 2–5 RP (RP_G≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RP_G≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RP_G≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RP_G≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.     

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Radiation-induced lung injury (RILI) is commonly observed in patients receiving radiotherapy, and clinical prevention and treatment remain difficult. We investigated the effect and mechanism of nicaraven for mitigating RILI. C57BL/6 N mice (12-week-old) were treated daily with 6 Gy X-ray thoracic radiation for 5 days in sequences (cumulative dose of 30 Gy), and nicaraven (50 mg/kg) or placebo was injected intraperitoneally in 10 min after each radiation exposure. Mice were sacrificed and lung tissues were collected for experimental assessments at the next day (acute phase) or 100 days (chronic phase) after the last radiation exposure. Of the acute phase, immunohistochemical analysis of lung tissues showed that radiation significantly induced DNA damage of the lung cells, increased the number of Sca-1⁺ stem cells, and induced the recruitment of CD11c⁺, F4/80⁺ and CD206⁺ inflammatory cells. However, all these changes in the irradiated lungs were effectively mitigated by nicaraven administration. Western blot analysis showed that nicaraven administration effectively attenuated the radiation-induced upregulation of NF-κB, TGF-β, and pSmad2 in lungs. Of the chronic phase, nicaraven administration effectively attenuated the radiation-induced enhancement of α-SMA expression and collagen deposition in lungs. In conclusion we find that nicaraven can effectively mitigate RILI by downregulating NF-κB and TGF-β/pSmad2 pathways to suppress the inflammatory response in the irradiated lungs.     

Effect of different treatment plans on irradiated small-bowel volume in gynecologic patients undergoing whole-pelvic irradiation

To evaluate the effect of different treatment plans for whole-pelvic irradiation on small-bowel volumes (SBVs) in patients with gynecologic malignancies, 40 patients were enrolled in this study. Computed tomography (CT) simulations were performed, and the small bowel of each patient was outlined manually. Treatment plans with equal-weighted (EW) and non-equal-weighted (NEW) (70% in bilateral directions) techniques of four-field and intensity-modulated radiation therapy (IMRT) were performed. The V10–V100 represented the volume (cm³) at different levels of the prescribed doses (10–100%). The V10–V100 was compared among the different treatment planning techniques, and patients who were suitable for IMRT or NEW were identified. IMRT and NEW significantly reduced the V50–V100 and V40–V60 levels compared with EW, respectively. NEW caused a significant reduction in the V30–V60 levels in patients with a BMI ≥26 kg/m². Patients with IMRT demonstrated lower V70–V100 levels compared with those with NEW. In patients with a BMI ≥26 kg/m² or an age ≥55 years, lower V20–V50 levels were noted using NEW compared with IMRT. Treatment planning with larger weighting in the bilateral directions in four-field radiotherapy reduces the low-dose SBV in patients with gynecologic malignancies, especially in those with a high BMI or the elderly. IMRT effectively reduces high-dose SBV, especially in patients with a low BMI.     

Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.     

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.     

Comparison of dose–volume histograms between proton beam and X-ray conformal radiotherapy for locally advanced non-small-cell lung cancer

The purpose of this study was to compare the parameters of the dose–volume histogram (DVH) between proton beam therapy (PBT) and X-ray conformal radiotherapy (XCRT) for locally advanced non-small-cell lung cancer (NSCLC), according to the tumor conditions. A total of 35 patients having NSCLC treated with PBT were enrolled in this analysis. The numbers of TNM stage and lymph node status were IIB (n = 3), IIIA (n = 15) and IIIB (n = 17), and N0 (n = 2), N1 (n = 4), N2 (n = 17) and N3 (n = 12), respectively. Plans for XCRT were simulated based on the same CT, and the same clinical target volume (CTV) was used based on the actual PBT plan. The treatment dose was 74 Gy-equivalent dose (GyE) for the primary site and 66 GyE for positive lymph nodes. The parameters were then calculated according to the normal lung dose, and the irradiation volumes of the doses (Vx) were compared. We also evaluated the feasibility of both plans according to criteria: V5 ≥ 42%, V20 ≥ 25%, mean lung dose ≥ 20 Gy. The mean normal lung dose and V5 to V50 were significantly lower in PBT than in XCRT. The differences were greater with the more advanced nodal status and with the larger CTV. Furthermore, 45.7% of the X-ray plans were classified as inadequate according to the criteria, whereas 17.1% of the proton plans were considered unsuitable. The number of inadequate X-ray plans increased in cases with advanced nodal stage. This study indicated that some patients who cannot receive photon radiotherapy may be able to be treated using PBT.     

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.     

Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor

The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6–18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1–11.0) and 8.2% (95% CI, 2.9–17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP (P = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2–4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown (P = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors.     

Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student''s t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student''s t-test) was performed. The median follow-up time was 35 months. Late Grade 2–3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose–volume modeling to predict rectal complications after HT.     

Treatment outcomes using CyberKnife for brain metastases from lung cancer

We investigated the clinical outcomes following treatment using stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for brain metastases from lung cancer. A total of 67 patients with 109 brain metastases from lung cancer treated using CyberKnife between 1998 and 2011 were retrospectively analyzed. SRS (median dose, 24 Gy) was used to treat 79 lesions, and 3-fraction SRT (median dose, 30 Gy) was used to treat 30 lesions. The median follow-up time was 9.4 months (range, 0.4–125 months). The 1-year local control rate was 83.3%, and the 1-year distant brain failure rate was 30.1%. The median survival time was 13.1 months, and the 1- and 3-year overall survival (OS) rates were 54.8% and 25.9%, respectively. On multivariate analysis, three factors were found to be statistically significant predictors of OS: (i) presence of uncontrolled primary disease [hazard ratio (HR) = 3.04; P = 0.002]; (ii) Brinkman index (BI) ≥ 1000 (HR = 2.75; P = 0.007); and (iii) pulmonary metastases (HR = 3.54; P = 0.009). Radionecrosis and worsening of neurocognitive function after radiosurgery were observed in 5 (7%) and 3 (4%) patients, respectively. Our results indicated that SRS/SRT for brain metastases from lung cancer was effective. Uncontrolled primary disease, high BI, and pulmonary metastases at treatment were significant risk factors for OS.     

Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm³ (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0–19.7 cm³. There were 16 lesions with a V14 of ≥7.0 cm³, and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm³ exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.     

Differences in rates of radiation-induced true and false rib fractures after stereotactic body radiation therapy for Stage I primary lung cancer

The purpose of this study was to analyze the dosimetry and investigate the clinical outcomes of radiation-induced rib fractures (RIRFs) after stereotactic body radiotherapy (SBRT). A total of 126 patients with Stage I primary lung cancer treated with SBRT, who had undergone follow-up computed tomography (CT) at least 12 months after SBRT and who had no previous overlapping radiation exposure were included in the study. We used the Mantel–Haenszel method and multiple logistic regression analysis to compare risk factors. We analyzed D(0.5 cm³) (minimum absolute dose received by a 0.5-cm³ volume) and identified each rib that received a biologically effective dose (BED) (BED3, using the linear–quadratic (LQ) formulation assuming an α/β = 3) of at least 50 Gy. Of the 126 patients, 46 (37%) suffered a total of 77 RIRFs. The median interval from SBRT to RIRF detection was 15 months (range, 3–56 months). The 3-year cumulative probabilities were 45% (95% CI, 34–56%) and 3% (95% CI, 0–6%), for Grades 1 and 2 RIRFs, respectively. Multivariate analysis showed that tumor location was a statistically significant risk factor for the development of Grade 1 RIRFs. Of the 77 RIRFs, 71 (92%) developed in the true ribs (ribs 1–7), and the remaining six developed in the false ribs (ribs 8–12). The BED3 associated with 10% and 50% probabilities of RIRF were 55 and 210 Gy to the true ribs and 240 and 260 Gy to the false ribs. We conclude that RIRFs develop more frequently in true ribs than in false ribs.     

A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose–volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm³ (30.5%) and 5.4 cm³ (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6–5.9 Gy, P < 0.001 and 2.1–9.9 Gy, P < 0.001, respectively). The D_mean of the contralateral parotid decreased in 70% of the patients (range, 0.2–4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC.     

Residential Traffic Exposure,Pulse Pressure,and C-reactive Protein: Consistency and Contrast among Exposure Characterization Methods

Background

Traffic exposure may increase cardiovascular disease (CVD) risk via systemic inflammation and elevated blood pressure, two important clinical markers for managing disease progression.

Objectives

We assessed degree and consistency of association between traffic exposure indicators as predictors of C-reactive protein (CRP) and pulse pressure (PP) in an adult U.S. Puerto Rican population (n = 1,017).

Methods

Cross-sectional information on health and demographics and blood data was collected. Using multiple linear regression, we tested for associations between CRP, PP, and six traffic exposure indicators including residential proximity to roads with > 20,000 vehicles/day and traffic density [vehicle miles traveled per square mile (VMT/mi²)]. Diabetes and obesity [body mass index (BMI) ≥ 30 kg/m²] were tested as effect modifiers.

Results

CRP was positively associated with traffic density in the total population [36% CRP difference with 95% confidence interval (CI) 2.5–81%] for residence within the highest versus lowest VMT/mi² level. With BMI ≥ 30, CRP showed significant positive associations with five of six traffic indices including residence ≤ 200 m versus > 200 m of a roadway [22.7% CRP difference (95% CI, 3.15–46.1)] and traffic density in the third highest versus lowest VMT/mi² level [28.1% difference (95% CI, 1.0–62.6)]. PP was positively associated with residence within ≤ 100 m of a roadway for the total population [2.2 mmHg (95% CI, 0.13–4.3 mmHg)] and persons with BMI ≥ 30 [3.8 mmHg (95% CI, 0.88–6.8)]. Effect estimates approximately doubled for residence within ≤ 200 m of two or more roadways, particularly in persons with diabetes [8.1 mmHg (95% CI, 2.2–14.1)].

Conclusions

Traffic exposure at roadway volumes as low as 20,000–40,000 vehicles/day may increase CVD risk through adverse effects on blood pressure and inflammation. Individuals with elevated inflammation profiles, that is, BMI ≥ 30, may be more susceptible to the effects of traffic exposure.     

肺癌患者三维适形放疗前后肺功能的动态变化及与放射性肺炎发生的关系研究

目的探讨非小细胞肺癌三维适形放疗前后肺功能的动态变化及其与放射性肺炎发生率的关系。方法68例未手术的肺癌患者,男42例,女26例,中位年龄52岁,KPS评分≥80分,均行三维适形放疗,放疗前及放疗后1、3个月检查肺功能主要参数用力肺活量（FVC）、1S用力呼气量（FEV1）、肺一氧化碳弥散量（CLCO）,同时观察放射性肺炎的发生率及程度。结果所有患者均完成放疗,剂量为60～70Gy。24例患者发生不同程度放射性肺炎,其中I级11例,Ⅱ级7例,Ⅲ级3例,Ⅳ级3例,无V级病例。FVC放疗前与放疗后3个月0级（n=44）和I＋Ⅱ＋Ⅲ＋Ⅳ级（n：24）放射性肺炎者比较,差异无统计学意义（P〉0．05）,而FEVl．0和DLCO放疗前与放疗后3个月的0级（n=44）和I＋Ⅱ＋Ⅲ级＋Ⅳ级（n=24）放射性肺炎者比较,差异有统计学意义（P〈0．05）。V20,V30及MLD平均值越大,放射性肺炎程度越高：结论非小细胞肺癌放疗后DLCO水平显著降低,放射性肺炎患者FEVl和DLCO放疗后显著降低。V20,V30,及MLD可预测放射性肺炎发生。     

Comparison of Abdominal Visceral Adipose Tissue Area Measured by Computed Tomography with That Estimated by Bioelectrical Impedance Analysis Method in Korean Subjects

We evaluated the concordance between visceral fat area (VFA) estimated by bioelectrical impedance analysis (BIA) or computed tomography (CT) in Korean subjects with a wide range in age and body mass index (BMI). In 1006 individuals (mean age 55.2 ± 11.8 (19–87) years, mean BMI 26.0 ± 3.5 (17–46) kg/m², 48.9% men), VFA quantified by CT was compared with VFA using multifrequency BIA machines within 15 days. Concordance rates were compared by age or BMI using correlation analysis, Bland-Altman plots, and intraclass correlation coefficient (ICC). Using BIA data, we established a regression formula to reflect CT-VFA. The mean VFAs by CT and BIA were 131.9 ± 57.3 cm² and 110.5 ± 33.9 cm², respectively (r = 0.605, p < 0.001). The mean difference was 21.4 ± 45.6 cm², tending to increase with BMI. In women with BMI <25 kg/m² or age <50 years, the VFAs by BIA were similar to those by CT (ICC = 0.496 in BMI <25 kg/m² and ICC = 0.638 in age <50 years). However, the difference was greater in men with BMI ≥25 kg/m² or age ≥50 years. Applying our formula, the difference between estimations decreased to 0.2 ± 38.2cm². VFA estimated by BIA correlated well with that by CT, but a more accurate formula is needed to match CT data, particularly in older men or subjects with a high BMI.