10th Fraction Research Articles

A comparative study of GTV displacements of primary thoracic esophageal carcinoma based on repeated 4DCT scans during radiotherapy

Objective To investigate the target volume displacements of primary thoracic esophageal carcinoma (TEC) based on repeated enhanced four-dimensional computed tomography (4DCT) scans during fractionated radiotherapy.Methods Twenty-nine patients with TEC underwent enhanced 4DCT before and in the 10th,20th,and 30th fractions of radiotherapy to delineate the gross tumor volumes (GTVs) and internal gross tumor volumes (IGTVs) in all phases.The GTV displacements of upper,middle,or lower TEC in three-dimensional directions in each time of 4DCT were compared,and the GTV displacements of upper,middle,or lower TEC in the same direction in all 4DCT scans were also compared.The changes in the centroid positions and volumes of IGTV during radiotherapy were determined.Results For the patients with middle TEC,significant differences were found between the GTV displacements in leftright (LR) direction,anterior-posterior (AP) direction,and superor-inferior (SI) direction when 4DCT was performed before or in the 20th fraction of radiotherapy (P =0.000-0.016),and significant differences were found between the GTV displacements in SI direction and LR and AP directions when 4DCT was performed in the 10th fraction of radiotherapy (P =0.000-0.006).For the patients with lower TEC,there were significant differences between the GTV displacements in SI direction and AP direction when 4DCT was performed before or in the 10th or 20th fraction of radiotherapy (P =0.004-0.013).There were no significant differences between the GTV displacements in the same direction in all 4DCT scans (P =0.102-0.823).There were no significant changes in the centroid positions of IGTV during radiotherapy (P =0.6 8 9-0.999),and the most significant decreases in IGTV volumes were seen in the 20th fraction of radiotherapy (P =0.012-0.029).Conclusions Under free breathing,the GTV displacement of upper,middle,or lower TEC in the same direction shows no significant changes in different 4DCT scans during radiotherapy;the IGTV volumes decrease significantly in the 20th fraction of radiotherapy,but there are no significant changes in the centroid positions of IGTV during radiotherapy. Key words: Esophageal neoplasm/ radiotherapy; Tomography, X-ray computed, four-dimensional; Gross tumor volume; Intrafraction target displacement

A comparison of anatomical and dosimetric variations in the first 15 fractions, and between fractions 16 and 25, of intensity‐modulated radiotherapy for nasopharyngeal carcinoma*

The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity‐modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty‐three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p<0.05). Consequently, there was a significant reduction of the percentage of the volume receiving the prescribed dose (V100) of CTV1 and GTVnd, which was more prominent after the first 15 fractions treatment compared to that between fraction 16 and 25 (p<0.05). Additionally, there was a significant increase in the mean dose (Dmean) and percentage of volume receiving ≥30Gy(V30) to the bilateral parotid in the first 15 fractions (p<0.05), but not between fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p<0.05), the increase of the percent of spinal cord volume receiving ≥40Gy(V40) was significantly higher in the first 15 fractions compared to that between fraction 16and25(p<0.05). Based on the dose constraint criterion in the RTOG0225 protocol, a total 39.1%(9/23) of phantom plan 1 (generated by applying the beam configurations of the original IMRT treatment plan to the anatomy of the second CT scan) and 17.4%(4/23) of phantom 2 (generated by applying the beam configurations of the replan 1 to the anatomy of the third CT scan) were out of limit for the dose to the normal critical structures. In conclusion, our data indicated that anatomic changes resulted in more predominant dosimetric effects in the first 15 fractions, and between fractions 16 and 25, of IMRT.PACS number: 87.53.Bn, 87.55.de, 87.55.Qr

SU‐E‐CAMPUS‐T‐02: Dose Variation and Migration Rule of Parotid Gland During Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma

Purpose: To quantify the position of parotid gland (PG) and expound rule of volume and dose changes during the Course of intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma patients (NPC). Methods: A total of 141 CT images from 47 NPC patients (three images for each patient: acquired before treatment, at the 15th fraction and 25th fraction for each patient) who underwent radical IMRT were selected for this retrospective study. The distance between the lateral/medial aspects of PG and midline (DLM and DMM) at the level of odontoid process were measured. The parotid glands were divided into ipsilateral or contralateral base on with or without GTV contour. The variation between plan dose and actual dose were calculated. Results: The volume reduction of both PG was more in the second half of treatment(SHT) than in the first half of treatment(FHT) (4.68±3.23 cc Vs. 2.46 ±4.55cc for the right PG and 5.96±2.99cc Vs. 2.06 ±2.99cc for the left PG). But, the V30 of bilateral PG decreased more significantly in FHT than SHT( 5.10±16.04% Vs. 1.14 ±21.54% for the right PG and 6.87±15.58% Vs. 0.81 ±15.94cc for the left PG). And the volume of GTVnx and GTVnd decreased more significantly in FHT than SHT(8.23±13.61cc Vs.3.30±8.09cc and 10.27±13.27 Vs.4.88±8.41cc). The DLM and DMM of contralateral PG shifted all medially and laterally both FHT and SHT, respectively. The DLM of ipsilateral PG shifted more medially in the FHT(3.83±1.53mm) than SHT(1.65±2.04mm), and the DMM of ipsilateral PG shifted medially in the FHT(0.80±2.96mm), but laterally in the SHT(2.19±3.96mm). Conclusion: The reduction of GTV leads to the position change of the parotid gland, which appear more dramatic dose change of the parotid gland in the FHT than SHT. This study was supported by Enze Foundation 2013 and had no Disclosures and Conflict of Interest

Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer.

Many head‐and‐neck cancer (HNC) patients treated with radiotherapy suffer significant anatomical changes due to tumor shrinkage or weight loss. The purpose of this study was to assess dose changes over target volumes and organs at risk during intensity‐modulated radiotherapy for HNC patients. Sixteen HNC IMRT patients, all requiring bilateral neck irradiation, were enrolled in the study. A CTplan was performed and the initial dose distribution was calculated. During the treatment, two subsequent CTs at the 15th (CT15) and 25th (CT25) fractions were acquired. The initial plan was calculated on the CT15 and CT25, and dose‐volume differences related to the CTplan were assessed. For target volumes, mean values of nearmaximun absorbed dose (D2%) increased at the 25th fraction, and doses covering 95% and 98% of volume decreased significantly at the 15th fraction. Contralateral and ipsilateral parotid gland mean doses increased by 6.1% (range: ‐5.4, 23.5%) and 4.7% (range: ‐9.1, 22.3%), respectively, at CT25. The D2% in the spinal cord increased by 1.8 Gy at CT15. Mean absorbed dose increases at CT15 and CT25 were observed in: the lips, 3.8% and 5.3%; the oral cavity, 3.5% and 2.5%; and lower middle neck structure, 1.9% and 1.6%. Anatomical changes during treatment of HNC patients affect dose distribution and induce a loss of dose coverage to target volumes and an overdosage to critical structures. Appropriate organs at risk have to be contoured and monitored in order to know if the initial plan remains suitable during the course of the treatment. Reported dosimetric data can help to identify patients who could benefit from adaptive radiotherapy.PACS numbers: 87.53.Kn, 87.55.Dk

Adaptive off-line protocol for prostate external radiotherapy with cone beam computer tomography

The goal of this work was to prepare and to evaluate an off-line adaptive protocol for prostate teleradiotherapy with kilovoltage cone beam computer tomography (CBCT). Ten patients with localized prostate carcinoma treated with external beams underwent image-guided radiotherapy. In total, 162CBCT images were collected. Position of prostate and pubis symphysis (PS) with respect to the isocenter were measured off-line. Using the CBCT scans obtained in the first three fractions the average position of prostate in relation (AvPosPr) to PB was calculated. On each CBCT scan, the position of prostate with respect to AvPosPr was calculated and cumulative histogram of prostate displacement with respect to AvPosPr was prepared. Using this data, the adaptive protocol was prepared in which (1) based on the CBCT made in the first three fractions the AvPosPr to PS is obtained, (2) in all other fractions two orthogonal images are acquired and if for any direction set-up error exceeds 0.2cm the patient's position is corrected, and (3) additionally, the patient's position is corrected if the AvPosPr exceeds 0.2cm in any direction. To evaluate the adaptive protocol for 30consecutive patients, the CBCT was also made in 10th and 21st fraction. For the first 10patients, the results revealed that the prostate was displaced in relation to AvPosPr >0.7cm in the vertical and longitudinal directions only on 4 and 5images of 162CBCT images, respectively. For the lateral direction, this displacement was >0.3cm in one case. For the group of 30patients, displacement was never >0.7, and 0.3cm for the vertical and lateral directions. In two cases, displacements were >0.7cm for the longitudinal direction. Implementation of the proposed adaptive procedure based on the on-line set-up error elimination followed by a reduction of systematic internal error enables reducing the CTV-PTV margin to 0.7, 0.7, and 0.4cm for the vertical, longitudinal, and lateral directions, respectively.

Changes of the transverse diameter and volume and dosimetry before the 25th fraction during the course of intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma

To quantify changes of the transverse diameter and volume and dosimetry, and to illustrate the inferiority of non-replanning during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients. Fifty-three NPC patients who received IMRT in 33 fractions were enrolled in this prospective trial. Before the 25th fraction, a new simulation computed tomography (CT) scan was acquired for all patients. The dose-volume histograms of the phantom plan were compared with the initial plan. Significant reduction of the transverse diameter of the nasopharyngeal, the neck, and 2 parotid glands volume was observed on second CT compared with the first CT (mean reduction 7.48 ± 4.45 mm, 6.80 ± 15.14 mm, 5.70 ± 6.26 mL, and 5.04 ± 5.85 mL, respectively; p < 0.01). The maximum dose and V-40 of the spinal cord, mean dose, and V30 of the left and right parotid, and V-50 of the brain stem were increased significantly in the phantom plan compared with the initial plan (mean increase 4.75 ± 5.55 Gy, 7.18 ± 10.07%, 4.51 ± 8.55 Gy, 6.59 ± 17.82%, 5.33 ± 8.55 Gy, 11.68 ± 17.11% and 1.48 ± 3.67%, respectively; p < 0.01). On the basis of dose constraint criterion in the RTOG0225 protocol, the dose of the normal critical structures for 52.83% (28/53) of the phantom plans were out of limit compared with 1.89% (1/53) of the initial plans (p < 0.0001). Because of the significant change in anatomy and dose before the 25th fraction during IMRT, replanning should be necessary during IMRT with NPC.

Towards the Development of Fiber-Based Oxidovanadium(IV) Catalysts for the Oxidation of Thioanisole

The catalytic activity of a series of bis-coordi- nated oxidovanadium(IV) complexes with 2-(4,5-diphenyl- 1H-imidazol-2-yl)-4R-phenol ligands (R = NO2, Br, H, MeO) was investigated for the oxidation of thioanisole by hydrogen peroxide in acetonitrile at 25C. The substituent groups had a significant effect on the catalytic activity and followed the order NO2 ( Br ( H ( MeO, with the nitro (NO2) derivative achieving (99% conversion after 10 min while the methoxy (MeO) derivative yielded the same result in 60 min. The nitro- and methoxy-substituted homogeneous catalysts were incorporated into polystyrene and electrospun to form nonwoven mats with fiber diam- eters in the range 0.33-1.98 lm. These vanadium incor- porated fibers were subjected to a continuous flow system at a flow rate of 1 mL/h for the oxidation of thioanisole and the nitro-substituted catalyst showed excellent catalytic activity with conversions dropping from 99 to 93% in the 10th fraction while the drop was down to 88% for the methoxy-substituted catalyst.

Dosimetric evaluation of a three-phase adaptive radiotherapy for nasopharyngeal carcinoma using helical tomotherapy

Adaptive radiotherapy (ART) has been introduced to correct the radiation-induced anatomic changes in head and neck cases during a treatment course. This study evaluated the potential dosimetric benefits of applying a 3-phase adaptive radiotherapy protocol in nasopharyngeal carcinoma (NPC) patients compared with the nonadaptive single-phase treatment protocol. Ten NPC patients previously treated with this 3-phase radiation protocol using Hi-Art Tomotherapy were recruited. Two new plans, PII-ART and PIII-ART, were generated based on the up-to-date computed tomography (CT) images and contours and were used for treatment in phase two (PII; after 25th fraction) and phase three (PIII; after 35th fraction), respectively. To simulate the situation of no replanning, 2 hybrid plans denoted as PII-NART and PIII-NART were generated using the original contours pasted on the PII- and PIII-CT sets by CT-CT fusion. Dosimetric comparisons were made between the NART plans and the corresponding ART plans. In both PII- and PIII-NART plans, the doses to 95% of all the target volumes (D95) were increased with better dose uniformity, whereas the organs at risk (OARs) received higher doses compared with the corresponding ART plans. Without replanning, the total dose to 1% of brainstem and spinal cord (D1) significantly increased 7.87 ± 7.26% and 10.69 ± 6.72%, respectively (P = 0.011 and 0.001, respectively), in which 3 patients would have these structures overdosed when compared with those with two replannings. The total maximum doses to the optic chiasm and pituitary gland and the mean doses to the left and right parotid glands were increased by 10.50 ± 10.51%, 8.59 ± 6.10%, 3.03 ± 4.48%, and 2.24 ± 3.11%, respectively (P = 0.014, 0.003, 0.053, and 0.046, respectively). The 3-phase radiotherapy protocol showed improved dosimetric results to the critical structures while keeping satisfactory target dose coverage, which demonstrated the advantages of ART in helical tomotherapy of NPC.

Radiation dose response of normal lung assessed by Cone Beam CT – A potential tool for biologically adaptive radiation therapy

BackgroundDensity changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. MethodsA total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66Gy in 2Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. ResultsA dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. ConclusionsCBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

SU-E-T-811: A Comparative Study of Replanning at the Midcourse and the Latter Course during Intensity-Modulated Radiotherapy for Patients with Nasopharyngeal Carcinoma

Purpose: The aim of replanning at the midcourse and the latter course was to illustrate the superior timing of replanning during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients. Methods: Twenty-three NPC patients received IMRT in 33 fractions were enrolled. Each patient with two repeated CT scans before the 16 fraction and before the 25 fraction, respectively. The anatomic changes were determined in the three CT scans. The differences of the dose distribution were compared in inital plan vs. phantom plan 1 and replanning 1vs. phantom plan 2. Results: The mean decrements of the transverse diameter of nasopharyngeal level (d1) and the transverse diameter of the neck level (d2) were 4.66mm, 2.63mm and 7.94mm, 5.78mm before the 16th and 25th fraction. The target volume reduced mainly in the first half. The mean decrements of volume GTVnx and GTVnd were 12.20cc, 8.91cc and 18.25cc, 13.71cc before the 16th and 25th fraction. While the volume of the parotid glands reduced mainly in the second half. The mean decrements of the left and right parotid glands volume were 1.40cc, 1.98cc and 6.31cc, 6.08cc before the 16th and 25th fraction. But the dose changes of bilateral parotids were more prominent in the first half than in the second half. There was a statistically significant increase in the mean dose and V30 to the bilateral parotid only in the first half (P < 0.05). Based on dose constraint criterion in the RTOG0225 protocol, the dose of the normal critical structures for 39.13% (9/23) were out of limit comparing to in the first half than 17.39(4/23) in the second half. Conclusions: Replanning at the midcourse may reach more benefits both in the coverage of the targets and sparing of normal structures for NPC patients. This study was supported by Zhejiang Provincial Medical and Health science Foundation of China (2008B198).

Variability in Bladder Volumes of Full Bladders in Definitive Radiotherapy for Cases of Localized Prostate Cancer

To evaluate variation in bladder volume of full bladders in definitive radiotherapy for localized prostate cancer and to investigate potential predictors of increased bladder volume variations. In 40 patients, the bladder volume was measured with megavoltage computed tomography (MVCT) imaging performed just before irradiation during the administration of the 1st fraction (#1), the 10th fraction (#10), the 20th fraction (#20), and the 30th fraction (#30). Patients were instructed to avoid urinating for 60-90 minutes before the planning CT (pln-CT) scan and before daily irradiation. Patients were also encouraged to drink an unspecified volume of liquid that would result in a clear but tolerable urge to urinate. The population-mean bladder volume (±1SD) was 219 ml (±83 ml) at the planning CT scan (pln-CT), 186 ml (±96 ml) at #1, 149 ml (±73 ml) at #10, 137 ml (±59 ml) at #20, and 136 ml (±60 ml) at #30. The mean intrapatient variation in bladder volume (1 SD relative to the mean bladder volume of each patient) was 38% (range: 10-84%). The bladder volume at the pln-CT was correlated with the intrapatient variance in bladder volume with a correlation coefficient of 0.54 and p <0.001. We observed a significant decline in bladder volumes during the course of radiotherapy. The bladder volume at the pln-CT was a significant predictor of increased bladder volume variations.

Daily cone-beam computed tomography used to determine tumour shrinkage and localisation in lung cancer patients

Purpose/Objective. Daily Cone-beam computed tomography (CBCT) in room imaging is used to determine tumour shrinkage during a full radiotherapy (RT) course. In addition, relative interfractional tumour and lymph node motion is determined for each RT fraction. Material and methods. From November 2009 to March 2010, 20 consecutive lung cancer patients (14 NSCLC, 6 SCLC) were followed with daily CBCT during RT. The gross tumour volume for lung tumour (GTV-t) was visible in all daily CBCT scans and was delineated at the beginning, at the tenth and the 20th fraction, and at the end of treatment. Whenever visible, the gross tumour volume for lymph nodes (GTV-n) was also delineated. The GTV-t and GTV-n volumes were determined. All patients were setup according to an online bony anatomy match. Retrospectively, matching based on the internal target volume (ITV), the GTV-t or the GTV-n was performed. Results. In eight patients, we observed a significant GTV-t shrinkage (15–40%) from the planning CT until the last CBCT. Only five patients presented a significant shrinkage (21–37%) in the GTV-n. Using the daily CBCT imaging, it was found that the mean value of the difference between a setup using the skin tattoo and an online matching using the ITV was 7.3±2.9 mm (3D vector in the direction of ITV). The mean difference between the ITV and bony anatomy matching was 3.0±1.3 mm. Finally, the mean distance between the GTV-t and the GTV-N was 2.9±1.6 mm. Conclusion. One third of all patients with lung cancer undergoing chemo-RT achieved significant tumour shrinkage from planning CT until the end of the radiotherapy. Differences in GTV-t and GTV-n motion was observed and matching using the ITV including both GTV-t and GTV-n is therefore preferable.

Oral candidiasis in patients receiving radiation therapy for head and neck cancer

Objective To investigate oral candidiasis in patients with head and neck cancer before, during, and after radiation therapy, and to explore its association with clinical oropharyngeal symptoms. Study Design A cohort study. Setting University hospital. Subjects and Methods Subjects who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: an oral cavity irradiated group (OIRR group, n = 29) and an oral cavity nonirradiated group (ONIRR group, n = 17). A control group consisted of 18 healthy subjects. Patients were examined for signs of oral candidiasis before, during, immediately after, and one month after RT. Mouth and throat soreness (MTS), dysphagia, and xerostomia were evaluated by self-reported questionnaires, and associations between oral candidiasis and these symptoms were analyzed. Results The incidence of oral candidiasis during RT was significantly higher in the OIRR group (55.2%) than in the ONIRR group (11.8%). Similarly, the occurrence of xerostomia during RT was significantly higher in the OIRR group (86.2%) than in the ONIRR group (52.9%). In the OIRR group, the mean MTS score at the 20th fraction of RT was significantly higher in patients with candidiasis (mean ± SD, 5.8 ± 2.1) than in those with RT-induced mucositis without candidiasis (3.7 ± 2.0). In the OIRR group, 65.2 percent of patients who experienced dysphagia developed oral candidiasis, compared with only 10 percent in the ONIRR group. Conclusion Oral candidiasis concurrent with oral mucositis due to RT may increase oropharyngeal discomfort during RT.

Clinical Study of the Necessity of Replanning Before the 25th Fraction During the Course of Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

To quantify the target and normal structures on dose distributing variations during intensity-modulated radiotherapy (IMRT) and to assess the value of replanning for nasopharyngeal carcinoma (NPC) patients. Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was acquired for all patients. According to the dose constraint criterion in the Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was generated on the new simulation CT. With the Quality Assessment Center of a CORVUS 6.3 treatment planning system, a phantom plan was generated for each patient by applying the beam configurations of the initial plan to the anatomy of the new simulation CT. The dose-volume histograms of the phantom plan were compared with the replanning. The percentage of prescription dose delivered to the clinical target volume (CTV1) was significantly increased by 4.91% +/- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the left parotid, and V30 to the right parotid were significantly decreased by 5.00 +/- 9.23Gy, 4.23 +/- 10.03Gy, and 11.47% +/- 18.89% respectively in the replanning, compared with the phantom plan (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were out of limit for the dose to the normal critical structures, whereas no plan was out of limit in replanning (p < 0.001). Replanning for patients with NPC before the 25th fraction during IMRT helps to ensure adequate dose to the target volumes and safe doses to critical normal structures.

SU‐FF‐T‐96: Clinical Study of the Necessity of Replanning IMRT Treatment for Patients with Nasopharyngeal Carcinoma

Purpose: To investigate the necessity of replan for patients diagnosed with nasopharyngeal carcinoma (NPC) during IMRT treatment. Method and Materials: Twenty‐eight NPC patients treated with IMRT were selected in this study. The patients were prescribed of 70 to 76 Gy for Gross Tumor Volume (GTV) in 33 fraction treatment. Before the 25th fraction of the treatment, a new simulation CT were acquired for all the patients. GTV, Clinical Target Volume (CTV) and the surrounding critical normal structures in the new CT were manually delineated by the same oncologist for the original plan contouring. The original prescription dose for GTVnx, GTVnd, CTV1, CTV2 was 70∼76Gy, 66∼70Gy, 60∼66Gy, and 56∼60Gy respectively. The target dose distributions in the new CT were obtained after recalculating based on the original plan in CORVUS 6.3 treatment planning system. The doses of the spinal cord and parotid glands in two plans were quantified and compared, as well as for normal critical structures. Results: Significant decrease of the transverse diameter of the nasopharyngeal and the left and right parotid glands volume were observed before the 25th fraction, comparing to the original planning CT (p&lt;0.0001). The mean decreases were 6.60±4.28mm, 4.49±4.77cm3 and 3.44±3.62cm3 respectively. The maximum dose of the spinal cord, mean dose of the left and right parotid were increased significantly at the 25th fraction (p&lt;0.01). The mean of the increased dose were 5.18±8.41Gy, 4.15±9.21Gy and 5.29±9.278Gy respectively. Based on dose constraint criterion in the RTOG0225 protocol, the dose of the normal critical structures for 50%(14/28) of the regenerated plans were out of limit comparing to 3%(1/28) of the original plans (p&lt;0.0001). Conclusion: Based on our observation, it is necessary to replan for patients with NPC to cover the targets and spare normal critical structures.

Suppression of neuro-inflammatory signaling cascade by tocotrienol can prevent chronic alcohol-induced cognitive dysfunction in rats

Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative–nitrosative stress and activation of inflammatory cascade finally resulting in neuronal apoptosis and thus dementia. In the present study, we investigated the comparative effect of both the isoforms of vitamin E, α-tocopherol and tocotrienol against chronic alcohol-induced cognitive dysfunction in rats. Male Wistar rats were given ethanol (10 g/kg; oral gavage) for 10 weeks, and treated with α-tocopherol and tocotrienol for the same duration. The learning and memory behavior was assessed using Morris water maze and elevated plus maze test. The rats were sacrificed at the end of 10th week and cytoplasmic fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative–nitrosative stress parameters, tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β). From the 6th week onwards, ethanol-treated rats showed significant increase in transfer latency in both the behavioral paradigms which was coupled with enhanced acetylcholinesterase activity, increased oxidative–nitrosative stress, TNF-α and IL-1β levels in different brain regions of ethanol-treated rats. Co-administration of α-tocopherol as well as tocotrienol significantly and dose-dependently prevented these behavioral, biochemical and molecular changes in the brains of ethanol-treated rats. However, the effects were more pronounced with tocotrienol. The current study thus demonstrates the possible involvement of oxidative–nitrosative stress mediated activation of inflammatory cascade in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of vitamin E isoforms, of which tocotrienol being more potent, in preventing the cognitive deficits associated with chronic alcohol consumption.

The representitativeness of patient position during the first treatment fractions

Background. During external radiotherapy daily or even weekly image verification of the patient position might be problematic due to the resulting workload. Therefore it has been customary to perform image verification only at the first treatment fraction. In this study it is investigated whether the patient position uncertainty at the initial three treatment fractions is representative for the uncertainty throughout the treatment course. Methods. Seventy seven patients were treated using Elekta Synergy accelerators. The patients were immobilized during treatment by use of a customized VacFix™ bag and a mask of AquaPlast®. Cone beam CT (CBCT) scans were performed at fractions 1, 2, and 3 and at the 10th and 20th treatment fractions. Displacements in patient position, translational and rotational, have been measured by an image registration of the CBCT and the planning CT scan. The displacements data are evaluated retrospectively and the effect of Action Level (AL) image verification protocols based on sessions 1, 2, 3 are simulated. The resulting overall patient position uncertainties of the different protocols are evaluated at the 10th and 20th fractions. Results and conclusions. The differences between the addressed protocols are shown to be very small compared to the overall increase in patient position uncertainty during the treatment course. Thus the main problem in achieving the smallest possible uncertainty for the overall treatment is not the selection of ‘the best’ image verification protocol for the initial three fractions. The main challenge is that the overall patient position uncertainty increases during the treatment course. Information about the patient position during the first three fractions is therefore not representative for the overall patient position. For these types of patients and immobilization equipment it would consequently be an advantage to reduce the number of image verification sessions during the initial fractions and then compensate with additional imaging sessions during the remaining treatment course.

Pelvic radiotherapy and urine substance P levels

9607 Background: Pelvic radiotherapy is widely used for the treatment of malignancies localized in the pelvis. Urinary complications are the major side effects of pelvic radiation. Etiopathogenesis of the radiation-induced bladder toxicity is not known. Substance P (SP) which is found in sensory neurons is important in both motor functions and local regulation of immune response in the urinary bladder. There are no clinical studies examining the effects of pelvic radiotherapy on urine SP levels. Hence, the goal of this study was to determine the acute and sub acute effects of RT on SP levels in the urine. Methods: Sixty-three patients were enrolled in the study. Out of 63 patients 15 of them had endometrial, 12 of them had cervical, 12 of them had prostate and 24 of them had rectal carcinoma. Each patient received 2 Gy daily fractions and urine samples were obtained before first fraction, one hour after first, eighth and twenty-fifth fraction and twelve weeks after the completion of RT. Each patient was evaluated for urinary side effects weekly, according to RTOG toxicity criteria. SP levels were determined directly form urine samples by enzyme immune assay. Results: Urinary side effects were reported in 36 % of patients after eighth fraction while most patients developed side effects after 25th fraction. Specifically all the prostate patients had grade one or 2 toxicity while only 66% of the patients with endometrial carcinoma developed toxicity. 93% and 84 % of patients with cervical and rectal carcinoma respectively had toxicity. Radiotherapy altered SP levels in the urine in patients with urinary toxicity. SP levels were decreased in most patients. Specifically SP levels decreased markedly (> 70 %) in 14 %, 24 % and 17 %, and intermediately (50–70 %) in 22 %, 14 % and 19 % of patients after first, eighth and twenty-fifth fractions respectively. In a group of patients, SP levels were increased after RT. SP levels increased markedly (> 90 %) in 6 %, 18 % and 15 % after first, eighth and twenty-fifth fractions respectively. Intermediate increase (50–90 %) was observed in 4 %, 4 % and 6 % of patients after first, eighth and twenty-fifth fractions respectively. Conclusions: These results demonstrate that RT affects peptidergic neurons in the bladder and altered Substance P levels could be responsible from acute and late toxicities of RT. No significant financial relationships to disclose.

Healers, providers of complementary/ alternative medicine, may be dangerous to all oncological patients including themselves

6137 Background: It is well known that healers may be dangerous to patients with malignant oncological diseases. We had the possibility to examine, treat and follow-up 3 locally well-known healers from 3 towns of the Czech-Moravian Highland at our hospital in 1999–2000. Methods: Healers used for their clients following healing practices: the sensual establishing causes (”diagnosis“) of client's health problems, removal of a bad energy or pain with hands cleaned in water, providing positive energy, treatment with herbal mixtures and teas, homeopathy, etc. Currently used medical therapy was offered to all of them. Results: All three healers were females, aged 57–64 years at diagnosis who came with very advanced tumors after the 6–36 months of symptoms duration in which two had tried to cure themselves. The 64 year-old woman with breast cancer T4b N2 M1 (SKI, LYM) survived 13 months after radiotherapy plus tamoxifen. The 57 year-old female with breast cancer T4b N2 M0 and 60 year-old one with eosophageal cancer T4 N1 M1 (HEP) refused radiotherapy after the 5th (as well as FAC chemotherapy) and 10th fraction, respectively, and died within 3–4 months since diagnosis. Conclusions: 1. Healers did not diagnose their illness in spite of the long-term presence of sings and symptoms. 2. They came with the 6–36 months' delay to medical examination and thus their tumours were very advanced. at medical diagnosis. 3. They were not able to improve their health status with their own healing practices. 4. Two healers interrupted usual medical therapy shortly after its beginning and their survival was only 3–4 months since diagnosis while the third survived 13 months with this therapy. 5. All three began their healing practice after an experience in being a patient for 2 months to years for a serious illness. 6. They claimed that their main goal had been

Etk/Bmx Transactivates Vascular Endothelial Growth Factor 2 and Recruits Phosphatidylinositol 3-Kinase to Mediate the Tumor Necrosis Factor-induced Angiogenic Pathway

Tumor necrosis factor (TNF), via its receptor 2 (TNFR2), induces Etk (or Bmx) activation and Etk-dependent endothelial cell (EC) migration and tube formation. Because TNF receptor 2 lacks an intrinsic kinase activity, we examined the kinase(s) mediating TNF-induced Etk activation. TNF induces a coordinated phosphorylation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Etk, which is blocked by VEGFR2-specific inhibitors. In response to TNF, Etk and VEGFR2 form a complex resulting in a reciprocal activation between the two kinases. Subsequently, the downstream phosphatidylinositol 3-kinase (PI3K)-Akt signaling (but not signaling through phospholipase C-gamma) was initiated and directly led to TNF-induced EC migration, which was significantly inhibited by VEGFR2-, PI3K-, or Akt-specific inhibitors. Phosphorylation of VEGFR2 at Tyr-801 and Tyr-1175, the critical sites for VEGF-induced PI3K-Akt signaling, was not involved in TNF-mediated Akt activation. However, TNF induces phosphorylation of Etk at Tyr-566, directly mediating the recruitment of the p85 subunit of PI3K. Furthermore, TNF- but not VEGF-induced activation of VEGFR2, Akt, and EC migration are blunted in EC genetically deficient with Etk. Taken together, our data demonstrated that TNF induces transactivation between Etk and VEGFR2, and Etk directly activates PI3K-Akt angiogenic signaling independent of VEGF-induced VEGFR2-PI3K-Akt signaling pathway.