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At least 199 records · Page 11

Kinetics of Intratumoral Immune Cell Activation During Chemoradiation for Cervical Cancer

Radiation therapy has direct cytotoxic effects on tumor-infiltrating lymphocytes, but it also has immune stimulatory effects that increase immune cell infiltration. The dynamics of these competing effects on immune cells at the site of the tumor are poorly characterized during chemoradiation treatment (CRT) because of the difficulty of obtaining consecutive tumor biopsies. We used a minimally invasive cervical cytobrushing method to analyze the kinetics of intratumoral immune cell changes in patients with cervical cancer during CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dosimetric Impact of Intrafraction Motion in Online-Adaptive Intensity Modulated Proton Therapy for Cervical Cancer

A method was recently developed for online-adaptive intensity modulated proton therapy (IMPT) in patients with cervical cancer. The advantage of this approach, relying on the use of tight margins, is challenged by the intrafraction target motion. The purpose of this study was to evaluate the dosimetric effect of intrafraction motion on the target owing to changes in bladder filling in patients with cervical cancer treated with online-adaptive IMPT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile

Cervical cancer represents the fourth most frequent malignancy in the world among women, and mortality has remained stable for the past 4 decades. Intravenous cisplatin with concurrent radiation therapy is the standard-of-care for patients with local and regional cervical cancer. However, cisplatin induces serious dose-limiting systemic toxicities and recurrence frequently occurs. In this study, we aimed to develop an intracervical drug delivery system that allows cisplatin release directly into the tumor and minimize systemic side effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantification of Dose-Volume and Dose-Length Parameters for Cervical Esophageal Stricture in Head and Neck Irradiation with the 3DCRT and IMRT Technique

To quantify and compare dose-volume and dose-length parameters of cervical esophagus between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) and to correlate with incidence of cervical strictures in head and neck cancer irradiation with radical intent.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effect of brachytherapy technique and patient characteristics on cervical cancer implant dosimetry

Our purpose was to evaluate the relationship between brachytherapy technique and patient characteristics on dose to organs-at-risk (OARs) in patients undergoing high dose rate (HDR) brachytherapy for cervical cancer. From 1998 to 2008, 31 patients with cervical cancer with full dosimetric data were identified who received definitive external-beam radiation and HDR brachytherapy with tandem and ovoid applicators. Doses were recorded at point A, the International Commission on Radiation Units and Measurements (ICRU)-38 rectal point, the ICRU-38 bladder point, the vaginal surface, and the pelvic sidewall. Generalized estimating equations were used to determine the significance of changes in OAR to point A dose ratios with differences in brachytherapy technique or patient characteristics. Patients underwent a median of 5 brachytherapy procedures (range, 3 to 5), with a total of 179 procedures for 31 patients. For all brachytherapy treatments, the average ratios between the doses for the rectal, bladder, vaginal surface, and pelvic sidewall reference points to those at point A were 0.49, 0.59, 1.15, and 0.17, respectively. In general, decreased OAR dose was associated with a lower stage, younger age, increased ovoid size, increased tandem length, and earlier implant number. Increased tandem curvature significantly increased bladder dose and decreased rectal dose. Intravenous anesthesia usage was not correlated with improved dosimetry. This study allowed identification of patient and procedure characteristics influencing OAR dosing. Although the advent of 3-dimensional (3D) image-guided brachytherapy will bring new advances in treatment optimization, the actual technique involved at the time of the brachytherapy implant procedure will remain important.

61 RADIATION PROTECTION AND DOSIMETRY↗

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

60 APPLIED LIFE SCIENCES↗

Gompertzian stochastic model with delay effect to cervical cancer growth

In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

60 APPLIED LIFE SCIENCES↗

A Gompertzian model with random effects to cervical cancer growth

In this paper, a Gompertzian model with random effects is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via maximum likehood estimation. We apply 4-stage Runge-Kutta (SRK4) for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of the cervical cancer growth. Low values of root mean-square error (RMSE) of Gompertzian model with random effect indicate good fits.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

The study included 26 patients with FIGO stage Ia1–Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The first experience of using {sup 99m}Tc-Al{sub 2}O{sub 3}-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

The purpose of the study was to evaluate the feasibility of using {sup 99m}Tc-Al{sub 2}O{sub 3}-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the {sup 99m}Tc-Al{sub 2}O{sub 3} in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) and 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer.

60 APPLIED LIFE SCIENCES↗

SU-E-T-36: An Investigation of the Margin From CTV to PTV Using Retraction Method for Cervical Carcinoma

Purpose: This work employs the retraction method to compute and evaluate the margin from CTV to PTV based on the influence of target dosimetry of setup errors during cervical carcinoma patients treatment. Methods: Sixteen patients with cervical cancer were treated by Elekta synergy and received a total of 305 KV-CBCT images. The iso-center of the initial plans were changed according to the setup errors to simulate radiotherapy and then recalculated the dose distribution using leaf sequences and MUs for individual plans. The margin from CTV to PTV will be concluded both by the method of retracting (Fixed the PTV of the original plan, and retract PTV a certain distance defined as simulative organization CTVnx. The minimum distance value from PTV to CTVnx which get specified doses, namely guarantee at least 99% CTV volume can receive the dose of 95%, is the margin CTV to PTV we found) and the former formula method. Results: (1)The setup errors of 16 patients in X, Y and Z directions were(1.13±2.94) mm,(−1.63±7.13) mm,(−0.65±2.25) mm. (2) The distance between CTVx and PTV was 5, 9 and 3mm in X, Y and Z directions According to 2.5+0.7σ. (3) Transplantation plans displayed 99% of CTVx10- CTVx7 and received 95% of prescription dose, but CTVx6- CTVx3 departed from standard of clinic.In order to protect normal tissues, we selected 7mm as the minimum value of the margin from CTV to PTV. Conclusion: We have test an retraction method for the margin from CTV to PTV evaluation. The retraction method is more reliable than the formula method for calculating the margin from the CTV to the PTV, because it represented practice of treatment, and increasing a new method in this field.

60 APPLIED LIFE SCIENCES↗

SU-E-T-263: Point Dose Variation Using a Single Ir-192 HDR Brachytherapy Plan for Two Treatments with a Single Tandem-Ovoid Insertion for Cervical Cancer

Purpose: To evaluate the point dose variations between Ir-192 HDR treatments on two consecutive days using a single tandem-ovoid insertion without replanning in cervical cancer patients. Methods: This study includes eleven cervical cancer patients undergoing HDR brachytherapy with a prescribed dose of 28 Gy in 4 fractions. Each patient had two tandemovoid insertions one week apart. Each insertion was treated on consecutive days with rescanning and replanning prior to each treatment. To study the effect of no replanning for day 2 treatments, the day 1 plan dwell position and dwell time with decay were applied to the day 2 CT dataset. The point dose variations on the prescription point H (defined according to American Brachytherapy Society), and normal tissue doses at point B, bladder, rectum and vaginal mucosa (based on ICRU Report 38) were obtained. Results: Without replanning, the mean point H dose variation was 4.6 ± 10.7% on the left; 2.3 ± 2.9% on the right. The mean B point variation was 3.8 ± 4.9% on the left; 3.6 ± 4.7% on the right. The variation in the left vaginal mucosal point was 12.2 ± 10.7%; 9.5 ± 12.5% on the right; the bladder point 5.5 ± 7.4%; and the rectal point 7.9 ± 9.1%. Conclusion: Without replanning, there are variations both in the prescription point and the normal tissue point doses. The latter can vary as much as 10% or more. This is likely due to the steep dose gradient from brachytherapy compounded by shifts in the positions of the applicator in relationship to the patients anatomy. Imaging prior to each treatment and replanning ensure effective and safe brachytherapy are recommended.

60 APPLIED LIFE SCIENCES↗

SU-E-T-507: Interfractional Variation of Fiducial Marker Position During HDR Brachytherapy with Cervical Interstitial Needle Template

Purpose: HDR brachytherapy using interstitial needle template for cervical cancer is commonly delivered in 4-5 fractions. Routine verification of needle positions before each fraction is often based on radiographic imaging of implanted fiducial markers. The current study evaluated interfractional displacement of implanted fiducial markers using CT images. Methods: 9 sequential patients with cervical interstitial needle implants were evaluated. The superior and inferior borders of the target volumes were defined by fiducial markers in planning CT. The implant position was verified with kV orthogonal images before each fraction. A second CT was acquired prior 3rd fraction (one or 2 days post planning CT). Distances from inferior and superior fiducial markers to pubic symphysis plane (perpendicular to vaginal obtulator)were measured. Distance from needle tip of a reference needle (next to the inferior marker) to the pubic symphysis plane was also determined. The difference in fiducial marker distance or needle tip distance between planning CT and CT prior 3rd fraction were measured to assess markers migration and needle displacement. Results: The mean inferior marker displacement was 4.5 mm and ranged 0.9 to 11.3 mm. The mean superior marker displacement was 2.7 mm and ranged 0 to 10.4 mm. There was a good association between inferior and superior marker displacement (r=0.95). Mean averaged inferior and superior marker displacement was 3.3 mm and ranged from 0.1 to 10.9 mm, with a standard deviation of 3.2 mm. The mean needle displacement was 5.6 mm and ranged 0.2 to 15.6 mm. Needle displacements were reduced (p<0.05) after adjusting according to needle-to-fiducials distance. Conclusion: There were small fiducial marker displacements between HDR fractions. Our study suggests a target margin of 9.7 mm to cover interfractional marker displacements (in 95% cases) for pretreatment verification based on radiographic imaging.

60 APPLIED LIFE SCIENCES↗

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose received by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.

60 APPLIED LIFE SCIENCES↗

SU-E-T-617: A Feasibility Study of Navigation Based Multi Criteria Optimization for Advanced Cervical Cancer IMRT Planning

Purpose: This study aims to validate multi-criteria optimization (MCO) against standard intensity modulated radiation therapy (IMRT) optimization for advanced cervical cancer in RayStation (v2.4, RaySearch Laboratories, Sweden). Methods: 10 advanced cervical cancer patients IMRT plans were randomly selected, these plans were designed with step and shoot optimization, new plans were then designed with MCO based on these plans,while keeping optimization conditions unchanged,comparison was made between both kinds of plans including the dose volume histogram parameters of PTV and OAR,and were analysed by pairing-t test. Results: We normalize the plan so that 95% volume of PTV achieved the prescribed dose(50Gy). The volume of radiation 10, 20, 30, and 40 Gy of the rectum were reduced by 14.7%,26.8%,21.1%,10.5% respectively(P≥0.05). The mean dose of rectum were reduced by 7.2Gy(P≤0.05). There were no significant differences for the dosimetric parameters for the bladder. Conclusion: In comparision with standard IMRT optimization, MCO reduces the dose of organs at risk with the same PTV coverage,but the result needs further clinical evalution.

60 APPLIED LIFE SCIENCES↗

SU-C-16A-07: Sculpting Isodose Lines: Design of An Internally Shielded Tandem for Cervical Cancer Brachytherapy

Purpose: With the prescription method moving from point A to 3D volume based in cervical cancer HDR brachytherapy, the traditional pear-shaped isodose lines are desired to be sculptured to conform to the irregular shaped target. The standard single channel tandem cannot generate asymmetric isodose lines. Most of the directionally shielded sources proposed in literature are challenging to manufacture and operate. In this study, we proposed a novel internally shielded tandem applicator design which gave users more freedom to manipulate isodose lines while planning. Methods: The proposed tandem design has one centrally located lead cylindrical rod of 8 mm in diameter serving as the internal shield. Multiple source channels with the diameter of 2 mm are evenly spaced and engraved on the central cylindrical rod. The overall diameter of the tandem with polymer encapsulation was kept to be 10 mm. Various number of channels and engraving depths have been tested in the design process. Geant4 Monte Carlo toolkit was used for dose calculation assuming a Varian VS2000 source was placed inside the applicator. A Monte Carlo based planning system has been developed in-house to generate brachytherapy plans. Test plans by using this internally shielded tandem were generated for 3 clinical cases. Results: Water phantom results shown the dose distribution from a VS2000 source in the tandem was strongly distorted towards one direction due to the presence of shielding material. Conformal plans with asymmetric isodose distributions around the tandem can be generated by optimizing dwell times in different channels. Conclusion: An effective and easy-to-use internally shielded tandem was developed. It gave user the freedom to sculpt isodose lines to generate conformal plans for cervical cancer brachytherapy.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-J-243: Reproducibility of Radiomics Features Through Different Voxel Discretization Levels in F18-FDG PET Images of Cervical Cancer

Purpose: Site-specific investigations of the role of Radiomics in cancer diagnosis and therapy are needed. We report of the reproducibility of quantitative image features over different discrete voxel levels in PET/CT images of cervical cancer. Methods: Our dataset consisted of the pretreatment PET/CT scans from a cohort of 76 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 31–76 years, treated with external beam radiation therapy to a dose range between 45–50.4 Gy (median dose: 45 Gy), concurrent cisplatin chemotherapy and MRI-based Brachytherapy to a dose of 20–30 Gy (median total dose: 28 Gy). Two board certified radiation oncologists delineated Metabolic Tumor volume (MTV) for each patient. Radiomics features were extracted based on 32, 64, 128 and 256 discretization levels (DL). The 64 level was chosen to be the reference DL. Features were calculated based on Co-occurrence (COM), Gray Level Size Zone (GLSZM) and Run-Length (RLM) matrices. Mean Percentage Differences (Δ) of features for discrete levels were determined. Normality distribution of Δ was tested using Kolomogorov - Smirnov test. Bland-Altman test was used to investigate differences between feature values measured on different DL. The mean, standard deviation and upper/lower value limits for each pair of DL were calculated. Interclass Correlation Coefficient (ICC) analysis was performed to examine the reliability of repeated measures within the context of the test re-test format. Results: 3 global and 5 regional features out of 48 features showed distribution not significantly different from a normal one. The reproducible features passed the normality test. Only 5 reproducible results were reliable, ICC range 0.7 – 0.99. Conclusion: Most of the radiomics features tested showed sensitivity to voxel level discretization between (32 – 256). Only 4 GLSZM, 3 COM and 1 RLM showed insensitivity towards mentioned discrete levels.

60 APPLIED LIFE SCIENCES↗