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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study

Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and Materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Image Guided Cervical Brachytherapy: 2014 Survey of the American Brachytherapy Society

Purpose: To provide an update of the 2007 American brachytherapy survey on image-based brachytherapy, which showed that in the setting of treatment planning for gynecologic brachytherapy, although computed tomography (CT) was often used for treatment planning, most brachytherapists used point A for dose specification. Methods and Materials: A 45-question electronic survey on cervical cancer brachytherapy practice patterns was sent to all American Brachytherapy Society members and additional radiation oncologists and physicists based in the United States between January and September 2014. Responses from the 2007 survey and the present survey were compared using the χ{sup 2} test. Results: There were 370 respondents. Of those, only respondents, not in training, who treat more than 1 cervical cancer patient per year and practice in the United States, were included in the analysis (219). For dose specification to the target (cervix and tumor), 95% always use CT, and 34% always use MRI. However, 46% use point A only for dose specification to the target. There was a lot of variation in parameters used for dose evaluation of target volume and normal tissues. Compared with the 2007 survey, use of MRI has increased from 2% to 34% (P<.0001) for dose specification to the target. Use of volume-based dose delineation to the target has increased from 14% to 52% (P<.0001). Conclusion: Although use of image-based brachytherapy has increased in the United States since the 2007 survey, there is room for further growth, particularly with the use of MRI. This increase may be in part due to educational initiatives. However, there is still significant heterogeneity in brachytherapy practice in the United States, and future efforts should be geared toward standardizing treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

Purpose: This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials: In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population. Results: General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea). Conclusions: This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of reference data. Several tumor-related symptoms resolved after treatment, and functioning and general QoL returned to that of the level of the reference population, indicating a transient impact of diagnosis and treatment. However, several treatment-related symptoms and problems did develop and persist, either immediately or gradually after treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Direction Modulated Brachytherapy for Treatment of Cervical Cancer. II: Comparative Planning Study With Intracavitary and Intracavitary–Interstitial Techniques

Purpose: To perform a comprehensive comparative planning study evaluating the utility of the proposed direction modulated brachytherapy (DMBT) tandem applicator against standard applicators, in the setting of image guided adaptive brachytherapy of cervical cancer. Methods and Materials: A detailed conceptual article was published in 2014. The proposed DMBT tandem applicator has 6 peripheral grooves of 1.3-mm width, along a 5.4-mm-thick nonmagnetic tungsten alloy rod of density 18.0 g/cm{sup 3}, capable of generating directional dose profiles. We performed a comparative planning study with 45 cervical cancer patients enrolled consecutively in the prospective observational EMBRACE study. In all patients, MRI-based planning was performed while utilizing various tandem-ring (27 patients) and tandem-ring-needles (18 patients) applicators, in accordance with the Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology recommendations. For unbiased comparisons, all cases were replanned with an in-house–developed inverse optimization code while enforcing a uniform set of constraints that are reflective of the clinical practice. All plans were normalized to the same high-risk clinical target volume D90 values achieved in the original clinical plans. Results: In general, if the standard tandem was replaced with the DMBT tandem while maintaining all other planning conditions the same, there was consistent improvement in the plan quality. For example, among the 18 tandem-ring-needles cases, the average D2cm{sup 3} reductions achieved were −2.48% ± 11.03%, −4.45% ± 5.24%, and −5.66% ± 6.43% for the bladder, rectum, and sigmoid, respectively. An opportunity may also exist in avoiding use of needles altogether for when the total number of needles required is small (approximately 2 to 3 needles or less), if DMBT tandem is used. Conclusions: Integrating the novel DMBT tandem onto both intracavitary and intracavitary–interstitial applicator assembly enabled consistent improvement in the sparing of the OARs, over a standard “single-channel” tandem, though individual variations in benefit were considerable. Although at an early stage of development, the DMBT concept design is demonstrated to be useful and pragmatic for potential clinical translation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Comparison of Computed Tomography– and Magnetic Resonance Imaging–based Clinical Target Volume Contours at Brachytherapy for Cervical Cancer

Purpose: We prospectively compared computed tomography (CT)– and magnetic resonance imaging (MRI)–based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. Methods and Materials: Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identified the clinical and tumor factors associated with (1) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and (2) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. Results: Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm{sup 3}) was larger than the mean MRI HR-CTV volume (35.1 cm{sup 3}; P<.0001, paired t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours (P<.02 for both). In addition, the spatial agreement (as measured by DC) between the HR-CTV contours decreased with an increasing BMI (P=.013). Conclusions: We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patients treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response. Conclusion: Patients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extrapelvic compensatory response, which may lead to increased hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

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↗
DOE OSTI2021

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↗
DOE OSTI2021

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↗
DOE OSTI2017

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↗
DOE OSTI2016

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↗
DOE OSTI2015

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↗
DOE OSTI2015

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↗
DOE OSTI2016

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↗
DOE OSTI2016

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↗
DOE OSTI2014

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↗
DOE OSTI2014

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↗
DOE OSTI2014

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↗