Browsing by Subject "Uterine Cervical Neoplasms"
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Item Analysis of Cervical Tumor Metabolism and Design of Magnetic Resonance Imaging Sequences for Abdominal and Pelvic Tissue/Tumor Hypoxia Studies(2012-11-19) Ding, Yao 1971-; Lewis, Matthew Allen; McColl, Roderick W.; Mason, Ralph P.; Zhao, Dawen; Lenkinski, RobertTumor oxygenation is increasingly recognized as an important factor to enhance the efficacy of chemo- and radiotherapy. MRI is becoming a widely accepted diagnostic imaging modality for investigation of tumor oxygenation. Research to improve the effectiveness of MR techniques for detection of oxygenation biomarkers (T1 and T2*) in the tissue/tumor hypoxia studies mainly includes efforts to improve sensitivity, efficiency and accuracy of measurements and to minimize scan duration. This dissertation mainly focuses on the development of novel combined multi-parametric techniques to obtain both BOLD and TOLD images simultaneously. A novel approach (ms-mGEPI-T1,2*) is developed to simultaneously measure both T1- and T2*-weighted signal changes, as well as and T1- and T2*-maps serially during a single dynamic MRI scan. This method has also been validated in both phantom and human abdominal tissue experiments and both in vitro and in vivo results are in good agreement with those obtained using conventional methods and the literature. The ms-mGEPI-T1,2* has been found to provide sensitive BOLD and TOLD responses under an oxygen challenge. Two enhanced versions of the ms-mGEPI-T1,2* technique with higher temporal resolution (SR-based sequence) or more accurate relaxation time estimation (IR-based sequence) are developed and validated in phantom and 3 volunteer studies. Relaxation times measured by these novel methods were in good agreement with those obtained using conventional pulse sequences. A pulse sequence which combines all three methods was developed for use on Philips MR user interface and has great potential in clinical MR examinations.Item The Art of Viral Oncogenesis: Lessons from Human Papillomavirus and Polyomavirus Transformed Cancers(2020-05-01T05:00:00.000Z) Zhao, Jiawei; Xu, Jian; Banaszynski, Laura; Pfeiffer, Julie K.; Wang, RichardViruses account for about 15% of all human cancer. Understanding viral oncogenesis can substantially broaden our general knowledge on the molecular mechanisms of carcinogenesis. In this dissertation, I focused on two types of DNA oncoviruses, human papillomavirus (HPV) and polyomavirus (HPyV), and identified novel mechanisms by which these two types of viruses cause human cancers. In HPV transformed cancer cells, I identified a novel circular RNA species, circE7, that spans and encodes the HPV E7 oncoprotein. I later demonstrated that circE7 translated E7 protein accounts for a substantial proportion of the E7 protein in a HPV transformed cancer cell line, and whose absence significantly impacts cancer cell proliferation in vitro and in vivo. In Merkel Cell Polyomavirus (MCPyV) transformed MCC cancer cells, I identified the activation of non-canonical NF-κB pathway activation by the MCPyV small T (ST) oncoprotein. I further demonstrated that the ectopically activated non-canonical NF-κB pathway is required for cell growth in low serum. The inhibition of non-canonical NF-κB signaling by a small peptide inhibitor also resulted in impaired cell growth in vitro and in vivo due to ER stress mediated apoptosis, suggesting a novel therapeutic intervention strategy for viral positive MCC (VP-CC) patients.Item Automated Treatment Planning in High Dose-Rate Brachytherapy for Cervical Cancer(2021-05-01T05:00:00.000Z) Gonzalez, Yesenia Amanda; Wang, Jing; Medin, Paul; Hrycushko, Brian; Albuquerque, KevinStandard care of cervical cancer is chemoradiation therapy followed by a boost to the cervix tumor site with High-dose-rate brachytherapy (HDRBT). HDRBT is a procedure that involves the insertion of radioactive sources into the tumorous area to ablate the cancer. Treatment planning for the procedure is typically performed on the day of treatment. The complex treatment planning process has led to issues such as prolonged treatment planning time and suboptimal plan quality. This dissertation reports systematic studies to improve treatment planning for HDRBT of cervical cancer. After a brief overview in Chapter 1, Chapter 2 will analyze the problems of sub-optimal plan quality and time management in the treatment planning workflow at our institution. In Chapter 3, developments on computational modules for automatic organ segmentation will be presented. Current clinical practice primarily relies on manual organ segmentation, but we have developed deep-learning models to segment the bladder, rectum, and sigmoid colon automatically, organs of particular importance for cervical cancer HDRBT. In Chapter 4, I present integration of the organ segmentation modules and other modules into the AutoBrachy system for clinical use to automate the planning process. Chapter 5 presents a deep-learning based method that can predict the physician's preference for a patient-specific treatment plan as defined by EQD2 to the bladder, rectum, sigmoid, and CTV D90. This method will serve as a guide in the future to automatically create patient-specific physician preferred treatment plans. Chapter 6 reports the study analyzing benefits from the use of joint intracavitary and interstitial HDRBT. Finally, Chapter 7 concludes the dissertation with discussions and future work.Item Cervical Cancer Treatment Pathway in Botswana(2021-05-01T05:00:00.000Z) Mehta, Priyanka Chetan; Grover, Surbhi; Nwachukwu, Chika; Kumar, KiranBACKGROUND: The incidence and mortality of cervical cancer in Botswana are among the highest in the world. Despite availability of chemoradiation and government funding for cancer treatment, many patients referred for chemoradiation in Botswana do not receive treatment. OBJECTIVES: This study sought to determine the proportion of cervical cancer patients referred for chemoradiation who do not receive cancer treatment and identify factors associated with receipt or non-receipt of treatment. Time between key steps in the care cascade was quantified to identify points that contribute to delays in care. This study also examined the impact of Princess Marina Hospital's multidisciplinary gynecologic oncology (PMH MDT) clinic on treatment receipt. METHODS: 230 patients with biopsy-proven cervical cancer were enrolled from January 2015 to July 2018 at Princess Marina Hospital in Gaborone, Botswana and followed until November 2019. Patient demographics, clinical characteristics, treatment characteristics, and time between steps in the care cascade were compared between treated and untreated patients using Wilcoxon rank sum tests, chi-squared tests, student's t tests, and univariate binomial logistic regression. RESULTS: 43 (18.7%) patients did not receive cancer treatment. Higher FIGO stage at initial presentation (OR: 0.50, 95% CI: 0.31-0.83, p < 0.01) and presentation during MDT clinic's first year (OR: 0.30, 95% CI: 0.15-0.59, p < 0.001) were associated with significantly lower odds of receiving treatment. Age, residential distance from treatment site, and HIV status were not predictive of treatment receipt. The largest discrepancy in time between treated and untreated patients was median time between pathology report and first MDT clinic visit: 22 days for treated patients (IQR: 9-63; n = 162) vs. 44 days for untreated patients (IQR: 9-146; n = 33) (p > 0.05). CONCLUSION: The MDT model is an evidence-based strategy to improve care coordination and reduce treatment disparities, thus improving outcomes for cancer patients. While there are still gaps in Botswana's cervical cancer care cascade, the PMH MDT clinic has led to significant improvements in cancer care among this population. The PMH MDT clinic provides strong evidence that MDT clinics can and should be established in under-resourced settings.Item Feasibility of Using Stereotactic Body Radiation as an Alternative to HDR for Treatment of Cervical Cancers(2006-08-11) Hesami, Homeira; Forster, KennethPurpose: Brachytherapy is frequently used to boost volumes at risk in the treatment of cervical cancers. Not all centers have HDR, or LDR capabilities, however, all have at least a linear accelerator. The possibility of using external beam radiation therapy utilizing a Stereotactic Body Radiation Therapy (SBRT) or Intensity Modulated SBRT (IM-SBRT) approach was evaluated in this project. Method and Materials: Volumes covered by the HDR prescription were used to define a Clinical Target Volume (CTV), with a prescription of 3250 cGy to the CTV over 5 fractions. Planning started with 33 equally spaced non-coplanar beams. Beam weight optimization was used to choose the most effective beam orientations. An SBRT plan was generated using unmodulated beams and then, by allowing beam modulation, IM-SBRT plans were generated. Minimum doses to 0.5, 1, 2, and 5 cc of rectum and bladder in the highest dose region were compared among HDR, SBRT, and IM-SBRT plans. Total Dose Volume Histograms (DVHs) were also compared. Results: 98% of the CTV was covered by the prescription dose for SBRT and IM-SBRT plans. Comparing plans, the highest doses to small volumes, showed that the dose to the high dose region of the rectum was increased by 8% for both SBRT and IM-SBRT plans, and the dose to the bladder was 8% higher using SBRT and 3% lower using IM-SBRT planning. The rectal DVHs for two patients were very similar for all three plans while IM SBRT showed an advantage for three patients. The bladder DVHs were similar for all plans for all patients. In general the rectum and bladder received a higher dose using SBRT, while the femoral heads received less dose using HDR. As expected, a larger volume of normal tissue was exposed to radiation using external beam irradiation. Conclusion: SBRT and IM-SBRT methods provided similar tumor coverage to HDR though normal structures received less dose using IM-SBRT approach than SBRT approach. It is feasible to replace HDR with external beam. This substitution makes the standard of care available to females worldwide and has the potential to treat large and irregularly shaped tumors.Item Knowledge and Perception of Cervical Cancer and Screening Programs of Women Seeking Care at Monduli Hospital in Tanzania and St. Paul Hospital in Addis Ababa, Ethiopia(2015-04-03) Ghidei, Luwam; Lea, JayanthiAlthough a 2010 survey assessing Tanzanian women's knowledge and attitude towards cervical cancer demonstrated over 75% of respondents correctly identified early marriage and multiparty, other studies demonstrated a lack of knowledge about cervical cancer screening and HPV transmission among patients and nurses. Additionally, many women in Tanzania are not readily represented in such questionnaires. Women who are able to attend clinics with screening programs are generally from higher socioeconomic backgrounds, younger, and more knowledgeable about cervical cancer.15 Educational programs focused on the importance of cervical screening in rural remote areas of Tanzania may have a positive impact on the early detection and identification of patients at early disease stage. Considering both Tanzania and Ethiopia had established VIA programs in 2011 (Figure 5), I developed a questionnaire to assess the knowledge and perception of cervical cancer and cervical cancer screening programs of women in Tanzania and Ethiopia to guide future cervical cancer prevention and screening educational programs in communities.Item Masking Enhances Accuracy of Bladder Deformation in Multi-Fraction Adaptive Brachytherapy as a First Step Toward Composite Dose Estimation(2014-02-04) Barclay, Jennifer; Albuquerque, Kevin; Pompos, Arnold; Gu, XuejunBACKGROUND: GEC-ESTRO guidelines for cervix HDR brachytherapy advocate measurement of the minimum dose to the 2cc volume of organs at risk (OAR) receiving the highest amount of radiation and summation across multiple treatment fractions to give a worst-case-scenario cumulative dose estimate. If the OAR from different fractions could be accurately co-registered using deformation, then a more accurate composite dose could be obtained. OBJECTIVE: As a first step toward composite dose estimation, we sought to assess and improve the quality of bladder deformation using a technique called masking, which involves resetting the pixel values within a contour. METHODS: CT scans from nine cervical cancer patients with bladders contoured by radiation oncologists were obtained, and the urethra near the bladder was contoured using the catheter as a fixed reference point. Three copies of each CT were made: the first was unaltered, the second had the bladder masked, and the third had the bladder masked at one pixel value and the rest of the body masked at a different pixel value. Using VelocityAI 2.8.1, the bladder was deformed onto the target (Fraction 1) planning CT from subsequent planning CTs in an attempt to match up the tissue from different fractions. To assess the accuracy of the deformation, several indices were used: the percent error of the deformed bladder volume from the expected volume, the conformality index, the Hausdorff distance, and the distance between the centers of the deformed urethra and the target urethra. RESULTS: Deformation quality improved with masking. The standard deviation of the percent error was reduced from 18.1% with no masking to 4.3% with masking. Mean conformality increased from 0.83 with no masking, to 0.91 with the bladder masked, to 0.93 with body and bladder masked (P<0.001). The mean Hausdorff distance decreased from 13.8mm without masking, to 9.1mm with the bladder masked, to 5.7mm with body and bladder masked (P<0.001). The mean error in the urethra deformation increased from 4.3mm without masking, to 5.2mm with the bladder masked, to 6.6mm with body and bladder masked (P=0.08). CONCLUSION: The accuracy of bladder deformation can be significantly improved by masking. With masking, the volume and location of the deformed bladder more closely approached that of the target bladder than without masking. Thus masking has the potential to improve the accuracy of dose deformation and composite dose calculation in adaptive brachytherapy.Item Noninvasive Assessment of Tumor Hypoxia Using MRI in Clinical and Preclinical Tumor Models(2013-01-16) Hallac, Rami R.; Mason, Ralph P.Tumor oxygenation influences response to radiation and plays important roles in malignant progression, angiogenesis and metastasis. While methods are available to quantitatively map pO2 dynamics in preclinical studies, new techniques are needed to noninvasively characterize tumor hypoxia and response to interventions in patients. Blood Oxygen Level Dependent (BOLD) MRI based on T2* contrast induced by deoxyhemoglobin concentration [dHb] is sensitive to tumor vascular oxygenation and blood flow. Meanwhile TOLD (Tissue Oxygen Level Dependent) MRI is sensitive to tissue oxygenation based on the shortening of the tissue water T1 due to molecular oxygen [O2]. In this study, I investigate the utility of BOLD and TOLD to evaluate tumor hypoxia in response to breathing hyperoxic gas in rats and test the feasibility of such measurements in patients. All MRI experiments were performed on either a 4.7T small animal Varian or a 3T clinical Philips scanner. Variation in BOLD and TOLD signal response observed in two syngeneic prostate tumor models: Dunning R3327-AT1 and -HI, with respect to oxygen and carbogen breathing were compared with quantitative change in pO2 measured using Fluorocarbon Relaxometry using Echo Planar Imaging for Dynamic Oxygen Mapping (FREDOM). In addition, BOLD and TOLD MRI measurements were used to predict radiation treatment outcome following a single dose of 30 Gy. BOLD MRI was also assessed in cervical cancer patients in response to breathing oxygen (15dm3/min). Two sequences were tested, multiple-shot EPI and multi echo gradient echo, to allow comparison. Significant correlations were found between BOLD and TOLD MRI and quantitative pO2 measurements for both oxygen and carbogen breathing. However, both gases had similar effect on modulating tumor hypoxia with no significant difference observed. The AT1 tumors showed a correlation between tumor growth delay for the animals breathing O2 during radiation and pre-irradiation TOLD responses to oxygen challenge. Finally, BOLD MRI at 3T was feasible for examining the potentially valuable biomarker of oxygenation seen in cervical cancer. Further parameters such as vascular perfusion and permeability based on DCE, cellularity based on diffusion, and TOLD response to oxygen challenge may also be readily incorporated into a dynamic evaluation.Item Predicting Severe Hematologic Toxicity from Extended-Field Chemoradiation of Para-Aortic Nodal Metastases from Cervical Cancer(2017-01-17) Yan, Kevin; Ramirez, Ezequiel; Gu, Xuejun; Albuquerque, KevinBACKGROUND AND PURPOSE: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients. MATERIAL AND METHODS: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively). CONCLUSIONS: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.Item A Ready Reference for Estimating Dose to Pelvic Node Metastases from High Dose Rate Brachytherapy (HDR-BT) in Cervical Cancer(2014-02-04) McKeever, Matthew R.; Hwang, Lindsay; Barclay, Jennifer; Dubas, Jeffrey; Xi, Yin; Bailey, April; Albuquerque, KevinINTRODUCTION: Metastasis to lymph nodes is one of the best predictive indicators of recurrence and death for cervical cancer patients. A dose of greater than 55 Gy is recommended for nodes 2 cm or less for durable control. It is expected that nodes closer to the radiation source will receive a higher dose. In this study we explored the relationship between lymph node location and the Point A dose as a means of assisting the radiation oncologist to determine the required boost dose. METHODS: This retrospective study from 2009 through 2013 included 29 cervical cancer patients receiving high dose rate brachytherapy and had a total of 60 metastases to pelvic lymph nodes. The lymph nodes were mapped and contoured in the treatment planning system.. The external beam and brachytherapy doses and percentage of brachytherapy point A dose received by each lymph node were calculated. RESULTS: The median doses from brachytherapy and external beam radiation to the lymph nodes were 5.5 Gy (range, 1.4-12.4 Gy) and 49.6 Gy (range, 42.5-62.9 Gy), respectively. The median total dose for all lymph nodes was 56.5 Gy (range, 46.5-66.3 Gy). The dose from brachytherapy accounted for 9.97% of the total dose to the lymph node. The location of the lymph node affected the dose received. The common iliac nodes, which were furthest from the uterus, received 3.18 Gy (11.09 % of point A); the internal iliac nodes received 4.29 Gy (16.43% of point A); and the external iliac nodes, which were closest to the uterus, received 6.05 Gy (21.75% of point A). As expected, nodes closer to the uterus received higher doses of brachytherapy radiation. DISCUSSION AND CONCLUSION: The common iliac nodes received the smallest fraction of the brachytherapy dose and thus need the greatest external boost dose. Also the internal iliac lymph nodes above the sacroiliac joint, the external iliac lymph nodes anterior to the acetabular line, and the external iliac nodes lateral to the external iliac artery received a smaller amount of the brachytherapy dose than the rest of the nodes in their group. This will require them to have a higher boost dose from external beam compared to other nodes in their group. The results of this study provide radiation oncologists a reference for determining which nodes require an external beam boost dose and the optimal boost dose for those nodes. Improved optimization of the boost dose should lead to better local control and outcomes for patients.Item [Southwestern News](2000-10-10) Harrell, Ann