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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

A real-time applicator position monitoring system for gynecologic intracavitary brachytherapy

Purpose: To develop a real-time applicator position monitoring system (RAPS) for intracavitary brachytherapy using an infrared camera and reflective markers. Methods: 3D image-guided brachytherapy requires high accuracy of applicator localization; however, applicator displacement can happen during patient transfer for imaging and treatment delivery. No continuous applicator position monitoring system is currently available. The RAPS system was developed for real-time applicator position monitoring without additional radiation dose to patients. It includes an infrared camera, reflective markers, an infrared illuminator, and image processing software. After reflective markers are firmly attached to the applicator and the patient body, applicator displacement can be measured by computing the relative change in distance between the markers. The reflective markers are magnetic resonance imaging (MRI) compatible, which is suitable for MRI-guided HDR brachytherapy paradigm. In our prototype, a Microsoft Kinect sensor with a resolution of 640 by 480 pixels is used as an infrared camera. A phantom study was carried out to compare RAPS' measurements with known displacements ranging from −15 to +15 mm. A reproducibility test was also conducted. Results: The RAPS can achieve 4 frames/s using a laptop with Intel{sup ®} Core™2 Duo processor. When the pixel size is 0.95 mm, the difference between RAPS' measurements and known shift values varied from 0 to 0.8 mm with the mean value of 0.1 mm and a standard deviation of 0.44 mm. The system reproducibility was within 0.6 mm after ten reposition trials. Conclusions: This work demonstrates the feasibility of a real-time infrared camera based gynecologic intracavitary brachytherapy applicator monitoring system. Less than 1 mm accuracy is achieved when using an off-the-shelf infrared camera.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Estimation of the Optimal Brachytherapy Utilization Rate in the Treatment of Gynecological Cancers and Comparison With Patterns of Care

Purpose: We aimed to estimate the optimal proportion of all gynecological cancers that should be treated with brachytherapy (BT)-the optimal brachytherapy utilization rate (BTU)-to compare this with actual gynecological BTU and to assess the effects of nonmedical factors on access to BT. Methods and Materials: The previously constructed inter/multinational guideline-based peer-reviewed models of optimal BTU for cancers of the uterine cervix, uterine corpus, and vagina were combined to estimate optimal BTU for all gynecological cancers. The robustness of the model was tested by univariate and multivariate sensitivity analyses. The resulting model was applied to New South Wales (NSW), the United States, and Western Europe. Actual BTU was determined for NSW by a retrospective patterns-of-care study of BT; for Western Europe from published reports; and for the United States from Surveillance, Epidemiology, and End Results data. Differences between optimal and actual BTU were assessed. The effect of nonmedical factors on access to BT in NSW were analyzed. Results: Gynecological BTU was as follows: NSW 28% optimal (95% confidence interval [CI] 26%-33%) compared with 14% actual; United States 30% optimal (95% CI 26%-34%) and 10% actual; and Western Europe 27% optimal (95% CI 25%-32%) and 16% actual. On multivariate analysis, NSW patients were more likely to undergo gynecological BT if residing in Area Health Service equipped with BT (odds ratio 1.76, P=.008) and if residing in socioeconomically disadvantaged postcodes (odds ratio 1.12, P=.05), but remoteness of residence was not significant. Conclusions: Gynecological BT is underutilized in NSW, Western Europe, and the United States given evidence-based guidelines. Access to BT equipment in NSW was significantly associated with higher utilization rates. Causes of underutilization elsewhere were undetermined. Our model of optimal BTU can be used as a quality assurance tool, providing an evidence-based benchmark against which actual patterns of practice can be measured. It can also be used to assist in determining the adequacy of BT resource allocation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Effectiveness of a genetic test panel designed for gynecological cancer: an exploratory study

To increase diagnostic efficiency and cost-effectiveness, we performed an exploratory genetic test using a newly designed panel containing 28 actionable and druggable genes, alterations in which are frequently reported in gynecological cancers (TANRE-G, Targeted variants ANalysis RElated to Gynecological cancers). Samples consisted of the formalin-fixed, paraffin-embedded tissue of endometrial (4 cases), cervical (3 cases), and ovarian (4 cases) carcinomas. The sequencing procedure was performed using Ion PGM in our institute with related sequencing kits, and data were analyzed using ClinVar. The present system achieved more than 2500 reads in all tumor samples, and enabled a copy number variation analysis. Results showed that actionable and druggable mutations were detected in 82% (9/11) and 64% (7/11) of cases, respectively, which was similar to other commercially available genetic tests. The amplification of MYC and KRAS was also detected. The analysis cost for each sample was JPY 94,000 (USD 850). These results demonstrate the potential of the TANRE-G panel as an effective tool for examining genetic alterations in gynecological cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Development of the M. D. Anderson Cancer Center Gynecologic Applicators for the Treatment of Cervical Cancer: Historical Analysis

Purpose: To provide historical background on the development and initial studies of the gynecological (gyn) applicators developed by Dr. Gilbert H. Fletcher, a radiation oncologist and chairperson from 1948 to 1981 of the department at the M.D. Anderson Hospital (MDAH) for Cancer Research in Houston, TX, and to acknowledge the previously unrecognized contribution that Dr. Leonard G. Grimmett, a radiation physicist and chairperson from 1949 to 1951 of the physics department at MDAH, made to the development of the gynecological applicators. Methods and Materials: We reviewed archival materials from the Historical Resource Center and from the Department of Radiation Physics at University of Texas M. D. Anderson Cancer Center, as well as contemporary published papers, to trace the history of the applicators. Conclusions: Dr. Fletcher's work was influenced by the work on gynecologic applicators in the 1940s in Europe, especially work done at the Royal Cancer Hospital in London. Those efforts influenced not only Dr. Fletcher's approach to the design of the applicators but also the methods used to perform in vivo measurements and determine the dose distribution. Much of the initial development of the dosimetry techniques and measurements at MDAH were carried out by Dr. Grimmett.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Relative Importance of Hip and Sacral Pain Among Long-Term Gynecological Cancer Survivors Treated With Pelvic Radiotherapy and Their Relationships to Mean Absorbed Doses

Purpose: To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs. Methods and Materials: We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2-15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors. Results: Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy. Conclusions: Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Optimal Patient Positioning (Prone Versus Supine) for VMAT in Gynecologic Cancer: A Dosimetric Study on the Effect of Different Margins

Purpose/Objective: It is unknown whether the historically found dosimetric advantages of treating gynecologic cancer with the patient in a prone position with use of a small-bowel displacement device (belly-board) remain when volumetric arc therapy (VMAT) is used and whether these advantages depend on the necessary margin between clinical target volume (CTV) and planning target volume (PTV). The aim of this study is to determine the best patient position (prone or supine) in terms of sparing organs at risk (OAR) for various CTV-to-PTV margins and VMAT dose delivery. Methods and Materials: In an institutional review board—approved study, 26 patients with gynecologic cancer scheduled for primary (9) or postoperative (17) radiation therapy were scanned in a prone position on a belly-board and in a supine position on the same day. The primary tumor CTV, nodal CTV, bladder, bowel, and rectum were delineated on both scans. The PTVs were created each with a different margin for the primary tumor and nodal CTV. The VMAT plans were generated with our in-house system for automated treatment planning. For all margin combinations, the supine and prone plans were compared with consideration of all OAR dose-volume parameters but with highest priority given to bowel cavity V{sub 45Gy} (cm{sup 3}). Results: For both groups, the prone position reduced the bowel cavity V{sub 45Gy}, in particular for nodal margins ≥10 mm (ΔV{sub 45Gy} = 23.9 ± 10.6 cm{sup 3}). However, for smaller margins, the advantage was much less pronounced (ΔV{sub 45Gy} = 6.5 ± 3.0 cm{sup 3}) and did not reach statistical significance. The rectum mean dose (D{sub mean}) was significantly lower (ΔD{sub mean} = 2.5 ± 0.3 Gy) in the prone position for both patient groups and for all margins, and the bladder D{sub mean} was significantly lower in the supine position (ΔD{sub mean} = 2.6 ± 0.4 Gy) only for the postoperative group. The advantage of the prone position was not present if it needed a larger margin than the supine position. Conclusion: For patients with gynecologic cancer, the historically found dosimetric advantages for the prone position remain for modern dose delivery techniques if large margins are needed. However, the advantage is lost for small margins and if the prone position needs a larger margin than the supine position.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

Purpose: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. Materials and methods: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipse treatment planning software. Patients were treated with a median radiation dose of 45 Gy (range: 37.5 to 50 Gy) to the primary volume and 45 Gy (range: 45 to 64.8 Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). Results: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45 Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months. Conclusion: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2018

Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 ± 2.04 mm, laterally 3.41 ± 3.62 mm, and anterior/posterior 3.86 ± 3.45 mm. The avg vector magnitude was 6.60 ± 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

SU-E-J-249: Characterization of Gynecological Tumor Heterogeneity Using Texture Analysis in the Context of An 18F-FDG PET Adaptive Protocol

Purpose: We propose a method to examine gynecological tumor heterogeneity using texture analysis in the context of an adaptive PET protocol in order to establish if texture metrics from baseline PET-CT predict tumor response better than SUV metrics alone as well as determine texture features correlating with tumor response during radiation therapy. Methods: This IRB approved protocol included 29 women with node positive gynecological cancers visible on FDG-PET treated with EBRT to the PET positive nodes. A baseline and intra-treatment PET-CT was obtained. Tumor outcome was determined based on RECIST on posttreatment PET-CT. Primary GTVs were segmented using 40% threshold and a semi-automatic gradient-based contouring tool, PET Edge (MIM Software Inc., Cleveland, OH). SUV histogram features, Metabolic Volume (MV), and Total Lesion Glycolysis (TLG) were calculated. Four 3D texture matrices describing local and regional relationships between voxel intensities in the GTV were generated: co-occurrence, run length, size zone, and neighborhood difference. From these, 39 texture features were calculated. Prognostic power of baseline features derived from gradientbased and threshold GTVs were determined using the Wilcoxon rank-sum test. Receiver Operating Characteristics and logistic regression was performed using JMP (SAS Institute Inc., Cary, NC) to find probabilities of predicting response. Changes in features during treatment were determined using the Wilcoxon signed-rank test. Results: Of the 29 patients, there were 16 complete responders, 7 partial responders, and 6 non-responders. Comparing CR/PR vs. NR for gradient-based GTVs, 7 texture values, TLG, and SUV kurtosis had a p < 0.05. Threshold GTVs yielded 4 texture features and TLG with p < 0.05. From baseline to intra-treatment, 14 texture features, SUVmean, SUVmax, MV, and TLG changed with p < 0.05. Conclusion: Texture analysis of PET imaged gynecological tumors is an effective method for early prognosis and should be used complimentary to SUV metrics, especially when using gradient based segmentation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Design and testing of a phantom and instrumented gynecological applicator based on GaN dosimeter for use in high dose rate brachytherapy quality assurance

Purpose: High dose rate brachytherapy (HDR-BT) is widely used to treat gynecologic, anal, prostate, head, neck, and breast cancers. These treatments are typically administered in large dose per fraction (>5 Gy) and with high-gradient-dose-distributions, with serious consequences in case of a treatment delivery error (e.g., on dwell position and dwell time). Thus, quality assurance (QA) or quality control (QC) should be systematically and independently implemented. This paper describes the design and testing of a phantom and an instrumented gynecological applicator for pretreatment QA and in vivo QC, respectively. Methods: The authors have designed a HDR-BT phantom equipped with four GaN-based dosimeters. The authors have also instrumented a commercial multichannel HDR-BT gynecological applicator by rigid incorporation of four GaN-based dosimeters in four channels. Specific methods based on the four GaN dosimeter responses are proposed for accurate determination of dwell time and dwell position inside phantom or applicator. The phantom and the applicator have been tested for HDR-BT QA in routine over two different periods: 29 and 15 days, respectively. Measurements in dwell position and time are compared to the treatment plan. A modified position–time gamma index is used to monitor the quality of treatment delivery. Results: The HDR-BT phantom and the instrumented applicator have been used to determine more than 900 dwell positions over the different testing periods. The errors between the planned and measured dwell positions are 0.11 ± 0.70 mm (1σ) and 0.01 ± 0.42 mm (1σ), with the phantom and the applicator, respectively. The dwell time errors for these positions do not exhibit significant bias, with a standard deviation of less than 100 ms for both systems. The modified position–time gamma index sets a threshold, determining whether the treatment run passes or fails. The error detectability of their systems has been evaluated through tests on intentionally introduced error protocols. With a detection threshold of 0.7 mm, the error detection rate on dwell position is 22% at 0.5 mm, 96% at 1 mm, and 100% at and beyond 1.5 mm. On dwell time with a dwell time threshold of 0.1 s, it is 90% at 0.2 s and 100% at and beyond 0.3 s. Conclusions: The proposed HDR-BT phantom and instrumented applicator have been tested and their main characteristics have been evaluated. These systems perform unsupervised measurements and analysis without prior treatment plan information. They allow independent verification of dwell position and time with accuracy of measurements comparable with other similar systems reported in the literature.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Adjuvant Intensity Modulated Whole-Abdominal Radiation Therapy for High-Risk Patients With Ovarian Cancer (International Federation of Gynecology and Obstetrics Stage III): First Results of a Prospective Phase 2 Study

Purpose: To assess treatment tolerance and toxicity rates of consolidative whole-abdominal radiation therapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high-risk patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III) using intensity modulated radiation therapy. Methods and Materials: The OVAR-IMRT-02 study is a multicenter, single-arm, phase 2 trial. Twenty patients with optimally debulked ovarian cancer (International Federation of Gynecology and Obstetrics stage III) with complete remission after chemotherapy were treated with intensity modulated WART as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy was applied to the entire peritoneal cavity. The primary endpoint was treatment tolerability, defined as lack of any Common Terminology Criteria for Adverse Events grade 4 toxicity within 10 weeks after start of treatment; secondary objectives were acute and chronic toxicity, quality of life, rates of therapy disruption and abortion, and progression-free and overall survival. Results: Intensity modulated WART resulted in excellent coverage of the whole peritoneal cavity, with effective sparing of all organs at risk. The primary analysis included all 20 enrolled patients, of whom 19 did not experience Common Terminology Criteria for Adverse Events grade 4 toxicity. Only 1 patient experienced acute grade 4 hematologic toxicity. Thus, the tolerability rate of intensity modulated WART was significantly higher than 70%. No gastrointestinal acute toxicities higher than grade 2 have been observed. During WART, mean global health status decreased by 18.1 points (95% confidence interval 7.1, 29.0). Six weeks after WART, global health status had already increased, with a mean score difference of 4.6 (95% confidence interval −11.1, 20.4) compared with baseline. Similar characteristics were observed for all function scale scores. Conclusion: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute toxicity and a treatment tolerability rate significantly higher than 70%. Together with our knowledge about clinical feasibility, meaning excellent coverage of the planning target volume and effective sparing of organs at risk, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Validation of mathematical models for the prediction of organs-at-risk dosimetric metrics in high-dose-rate gynecologic interstitial brachytherapy

Purpose: Given the complicated nature of an interstitial gynecologic brachytherapy treatment plan, the use of a quantitative tool to evaluate the quality of the achieved metrics compared to clinical practice would be advantageous. For this purpose, predictive mathematical models to predict the D{sub 2cc} of rectum and bladder in interstitial gynecologic brachytherapy are discussed and validated.Methods: Previous plans were used to establish the relationship between D2cc and the overlapping volume of the organ at risk with the targeted area (C0) or a 1-cm expansion of the target area (C1). Three mathematical models were evaluated: D{sub 2cc}=α*C{sub 1}+β (LIN); D{sub 2cc}=α– exp(–β*C{sub 0}) (EXP); and a mixed approach (MIX), where both C{sub 0} and C{sub 1} were inputs of the model. The parameters of the models were optimized on a training set of patient data, and the predictive error of each model (predicted D{sub 2cc}− real D{sub 2cc}) was calculated on a validation set of patient data. The data of 20 patients were used to perform a K-fold cross validation analysis, with K = 2, 4, 6, 8, 10, and 20.Results: MIX was associated with the smallest mean prediction error <6.4% for an 18-patient training set; LIN had an error <8.5%; EXP had an error <8.3%. Best case scenario analysis shows that an error ≤5% can be achieved for a ten-patient training set with MIX, an error ≤7.4% for LIN, and an error ≤6.9% for EXP. The error decreases with the increase in training set size, with the most marked decrease observed for MIX.Conclusions: The MIX model can predict the D{sub 2cc} of the organs at risk with an error lower than 5% with a training set of ten patients or greater. The model can be used in the development of quality assurance tools to identify treatment plans with suboptimal sparing of the organs at risk. It can also be used to improve preplanning and in the development of real-time intraoperative planning tools.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2019

Para-aortic Lymphadenectomy for Gynecologic Cancers: Introducing the “Trans-Retro-Peritoneal (TRP) Single-Port Access”

Background: In gynecological surgery to date, two distinct types of endoscopic accesses have been used to perform para-aortic lymphadenectomies: transperitoneal and extraperitoneal, each with advantages and disadvantages.{sup 1} We propose to develop a new mini-invasive access to perform an endoscopic extraperitoneal para-aortic lymphadenectomy via a single-port umbilical device that, to our knowledge, has never been described. Methods: This innovative approach combines both an extraperitoneal and intraperitoneal procedure via the same umbilical incision using one single trocar. A 3–4 cm trans-umbilical incision is performed and a three-channel single-port device (Gelpoint Mini°; Applied Medical, Rancho Santa Margarita, CA, USA) is introduced in the peritoneal cavity. After peritoneal exploration, the peritoneum overlying the aorta bifurcation is grabbed, raised to the umbilicus, opened, and the single-port device is then re-introduced into the retroperitoneal space. Results: The intervention has been successful in three patients with locally advanced cervical cancer (two International Federation of Gynecology and Obstetrics [FIGO] stage IB2, and one FIGO stage IVA) scheduled for concomitant radiochemotherapy after exclusion of any suspicious lymph nodes by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), according to our standards of practice based on the European Society of Gynaecological Oncology (ESGO) and National Comprehensive Cancer Network (NCCN) guidelines.{sup 2,3} Due to the type of cancer, lymphadenectomy was limited to the infra-mesenteric nodes,{sup 2,4} although the dissection went up to the left renal vein in each case. We retrieved 13, 20, and 25 lymph nodes. No complications occurred. Conclusions: We describe a promising technique that combines all the advantages of the two previously described accesses without their disadvantages, and with the cosmetic benefit of one almost invisible single trans-umbilical scar.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

International Brachytherapy Practice Patterns: A Survey of the Gynecologic Cancer Intergroup (GCIG)

Purpose: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). Methods and Materials: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. Results: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). Conclusion: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.

62 RADIOLOGY AND NUCLEAR MEDICINE↗