Active breathing control guided stereotactic body ablative radiotherapy for management of liver metastases from colorectal cancer.

Background: Liver metastases may occur during the course of several cancer types and may be associated with significant morbidity and mortality. There is paucity of data regarding the utility of Active Breathing Control (ABC) guided Stereotactic Ablative Body Radiotherapy (SABR) for management of Liver Metastases from Colorectal Cancer (LMCC). Our aim is to investigate the role of ABC guided SABR for management of liver metastases. Patients and methods: 42 liver metastases of 29 patients treated with ABC guided SABR between February 2015 and October 2018 were retrospectively assessed for local control (LC), overall survival (OS), and toxicity outcomes. Primary endpoint was LC. Secondary endpoints were OS and treatment toxicity. Results: At a median follow up duration of 16 months (range: 9-74 months), median OS was 20 months and 3 patients were still alive at last follow up. 1-year OS was 83% and 2-year OS was 28%. LC rates were 92% and 61% at 1 and 2 years, respectively. Comparative analysis of Biological Effective Dose (BED) values revealed that higher BED10 values were associated with higher LC rates (p=0.007). While LC rates for BED10 ≥ 100 Gray (Gy) were 94% and 86% at 1 and 2 years, corresponding LC rates for BED10 < 100 Gy were 89% and 36%, respectively with statistical significance (p=0.007). Assessment of acute and late toxicity outcomes revealed that most common toxicity was fatigue, however, no patients had ≥ grade 3 toxicity. Conclusion: ABC guided SABR is an effective and safe treatment modality for LMCC management.

Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.

The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.

The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1ß (TGF-1ß) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1ß levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Evaluation of treatment outcomes of early-stage endometrial cancer radiotherapy: a single center experience.

BACKGROUND: Postoperative adjuvant radiotherapy (RT) in the management of early stage endometrial cancer (EC) is still controversial. Here we report our institutional experience with patients who received postoperative RT for stage I-II EC over a period of 35 years and assess potential predictors of local recurrence (LR), distant metastasis (DM), and overall survival (OS). MATERIALS AND METHODS: A total of 188 patients undergoing postoperative RT for stage IA-II EC between 1977 and 2012 were evaluated. Some 96 received median 46 Gy whole pelvic radiotherapy (WPRT) (range: 40-60 Gy), 37 were given WPRT with vaginal cuff therapy (VCT), and 55 received only VCT either with brachytherapy (BT) or stereotactic body radiotherapy (SBRT). Chemotherapy was given to 5 patients with uterine papillary serous carcinoma (UPSC). Logistic regression analysis was used to assess the effect of clinicopathological factors on LR, DM, and OS. RESULTS: Median follow-up time was 11 years (range: 1-35 years). At the time of analysis, 34 patients were not alive. Of the 15 patients with LR, 7 (46.7%) recurred in the vaginal stump, 5 (33.3%) in the pelvic region, and 3 (20%) in the paraaortic nodal region, while 12 had distant metastasis. UPSC histology (p=0.027), sole VCT (p=0.041), high histologic grade (p=0.034), and age≥71 (p=0.04) were poor prognostic factors on univariate analysis. CONCLUSIONS: In our patients receiving radiotherapy for early-stage EC, grade III disease and age≥71 were associated with shorter OS whereas UPSC histology was an independent predictor for both LR and DM.

Efficacy of various irrigation protocols on the removal of triple antibiotic paste.

AIM: To compare the efficacy of irrigation protocols on the removal of triple antibiotic paste (metronidazole, ciprofloxacin and minocycline) (TAP) from artificial grooves in root canals. METHODOLOGY: Root canals in 72 extracted single-rooted teeth were prepared using ProTaper rotary instruments up to size F5. The roots were split longitudinally and a standardized groove was prepared in the apical part of one segment. TAP was placed in the grooves, and the root halves were reassembled. The roots were randomly divided into six experimental groups according to the irrigation protocol used: distilled water, 1% NaOCl, 2.5% NaOCl, 100% ethanol, 17% EDTA and passive ultrasonic irrigation (PUI) with 1% NaOCl. The root segments were disassembled, and the amount of TAP remaining was evaluated under a stereomicroscope at 20× magnification using a four-grade scoring system. The data were evaluated statistically using Kruskal-Wallis and Mann-Whitney U-tests with a 95% confidence level (P = 0.05). RESULTS: There were significant differences amongst the groups (P < 0.001). Passive ultrasonic irrigation (PUI) with 1% NaOCl removed significantly more TAP than the other irrigating solutions (P < 0.05). Distilled water, 1% NaOCl, ethanol and EDTA were associated with significantly more remaining TAP. CONCLUSIONS: PUI with 1% NaOCl was more effective in removing TAP from artificial grooves in root canals than other irrigating solutions without ultrasonic agitation. It was not possible completely to remove TAP from root canals.

Evaluation of linear accelerator-based stereotactic radiosurgery in the management of meningiomas: a single center experience.

PURPOSE: Stereotactic radiosurgery (SRS) has emerged as a viable alternative to surgery in the management of meningioma through exploiting the advantage of being minimally invasive with few complications and acceptable local control rates. The aim of this study was to evaluate the efficiency of linear accelerator (LINAC)-based SRS in the management of meningiomas and to report our experience using this sophisticated technique. METHODS: Between July 1998 and March 2012, 79 patients (42 female, 37 male) were treated using LINAC-based SRS in the Department of Radiation Oncology, Gulhane Military Medical Academy. Median dose was 13 Gy (range 10- 16) prescribed to the 80-95% isodose line encompassing the target. RESULTS: Median follow-up time was 53 months (range 9-112). Median tumor volume was 3.43 cc (range 0.3-14.1). Local tumor control was 89.7% in the 68 patients with adequate follow-up. CONCLUSION: LINAC-based SRS offers a safe and effective treatment alternative to surgery in intracranial meningiomas with high local control rates and low morbidity.

Evaluation of the role of radiotherapy in the management of dermatofibrosarcoma protuberans.

PURPOSE: The aim of this study was to evaluate the role of radiotherapy (RT) in the management of dermatofibrosarcoma protuberans (DFSP). METHODS: Twenty-eight patients treated with RT for DFSP between 1974 and 2012 at Gulhane Military Medical Academy (GMMA) Radiation Oncology Department were retrospectively evaluated. Twenty-five out of 28 patients (89%) received postoperative RT and 3 received definitive RT alone. In the 25 patients receiving postoperative RT, the type of surgical excision was limited excision in 5 patients and wide excision in the remaining 20. Median RT dose was 63.21±3.7 Gy (range 50-70). RESULTS: At a median follow-up of 5 years, 5-year overall survival (OS) for the whole patient group was 93%. No relationship was determined between the total delivered RT dose and OS. The 5-year OS of the 10 female patients was 90% whereas it was 94% for the 18 male patients (p>0.05). Five-year disease-free survival (DFS) for the patients undergoing wide excision with RT vs. those undergoing limited excision with RT was significantly superior (p <0.05) in patients treated with wide excision and RT. CONCLUSION: RT is an effective treatment option for DFSP patients with positive postoperative margins, recurrent disease and selected inoperable cases.

Evaluation of stereotactic body radiotherapy (SBRT) boost in the management of endometrial cancer.

The purpose of this study is to evaluate the use of linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) boost with multileaf collimator technique after pelvic radiotherapy (RT) in patients with endometrial cancer. Consecutive patients with endometrial cancer treated using LINAC-based SBRT boost after pelvic RT were enrolled in the study. All patients had undergone surgery including total abdominal hysterectomy and bilateral salpingo-oophorectomy ± pelvic/paraortic lymphadenectomy before RT. Prescribed external pelvic RT dose was 45 Gray (Gy) in 1.8 Gy daily fractions. All patients were treated with SBRT boost after pelvic RT. The prescribed SBRT boost dose to the upper two thirds of the vagina including the vaginal vault was 18 Gy delivered in 3 fractions with 1-week intervals. Gastrointestinal and genitourinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 3 (CTCAE v3).Between April 2010 and May 2011, 18 patients with stage I-III endometrial cancer were treated with LINAC-based SBRT boost after pelvic RT. At a median follow-up of 24 (8-26) months with magnetic resonance imaging (MRI) and gynecological examination, local control rate of the study group was 100 % with negligible acute and late toxicity.LINAC-based SBRT boost to the vaginal cuff is a feasible gynecological cancer treatment modality with excellent local control and minimal toxicity that may replace traditional brachytherapy boost in the management of endometrial cancer.

Evaluation of active breathing control-moderate deep inspiration breath-hold in definitive non-small cell lung cancer radiotherapy.

The purpose of this study is to evaluate the effect of Active Breathing Control-moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving ≥ 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes.

Tc-99m polyclonal human immunoglobulin G imaging in Graves' ophthalmopathy.

PURPOSE: The authors evaluated the utility of Tc-99m-labeled human immunglobulin G (HIG) in determining the severity of orbital inflammation and the relation of orbital Tc-99m HIG uptake and clinical parameters in patients with Graves' ophthalmopathy. MATERIALS AND METHODS: Images were obtained in 23 patients (13 women, 10 men; mean age, 51+/-10 years) with Graves' ophthalmopathy. Planar orbital images were obtained and SPECT was performed using a triple-detector gamma camera 4 hours after 370 MBq (10 mCi) Tc-99m HIG injection. Tc-99m HIG uptake was classified using transaxial and coronal slices as 1, mild; 2, moderate; and 3, severe. The clinical severity of orbital disease was categorized, according to the criteria described by Feldon and Unsold, as class I, mild involvement; class II, moderate; and class III, severe. Disease was considered to be clinically inactive if symptoms and signs were stable or improved in the last two examinations performed at least 6 months apart. RESULTS: Sixteen patients were clinically inactive, and seven patients were active. The mean Tc-99m HIG classes were 1.5+/-0.5 and 2.6+/-0.5, respectively (P = 0.02). There was not a good correlation between the clinical classification and Tc-99m HIG classification, whereas the presence of active disease showed a good correlation with Tc-99m HIG classification (r = 0.703; P = 0.0002). CONCLUSIONS: Tc-99m HIG imaging showed possible ongoing subclinical inflammation in the orbits of the patients with Graves' ophthalmopathy regardless of the clinical classification. Tc-99m HIG SPECT seems a promising procedure for evaluating the presence of active orbital inflammation.

Monitoring of genotoxic damage in smokeless tobacco ((Maras powder) consumers using micronucleated exfoliated oral cells.

Maras powder is a kind of smokeless tobacco used in the south-eastern region of Turkey. The present study was carried out to assess possible DNA damage in exfoliated oral cells of Maras powder users by analysing the frequencies of micronuclei (MN), which is a simple and reliable biomarker for genotoxic damage and to screen for the detection of site-specific differences in the frequencies of MN. The mean (±SD) MN frequency in the inner lip mucosa site was 1.27(±0.55) % for Maras powder users and 0.88(±0.47) % for non-smoking control subjects (p < 0.05) and 0.82(±0.40) % for the buccal site of Maras powder users (p < 0.01). There was no significant site-specific difference between the inner lip site and the buccal mucosa site 0.73(±0.43) % in the MN frequency of non-smoking control subjects (p > 0.05). There was no significant effect of daily consumption of Maras powder, and duration of usage on MN frequencies. The present study suggests that the oral use of smokeless tobacco represents a genotoxic hazard and also that use of MN from a single site may be misleading as a marker of genotoxic exposure. Habitual use of Maras powder should be taken into account and could be considered unsafe.