Browsing by Subject "Lymph Nodes"
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Item Identification of Drivers of Tumor Lymphangiogenesis in Non-Small Cell Lung Carcinoma (NSCLC)(2014-02-04) Sibley, Robert Carson; Dellinger, Michael; Brekken, RolfBACKGROUND: Non-small Cell Lung Carcinomas (NSCLCs) frequently spread to regional lymph nodes before they colonize other regions of the body, and the status of regional lymph nodes is an important prognostic factor for predicting the outcome of patients with lung cancer. It has recently been demonstrated that lymphangiogenesis, the sprouting of new lymphatic vessels from pre-existing vessels, facilitates the lymphogenous dissemination of NSCLC. However, the molecular mechanisms driving lymphangiogenesis in NSCLC are poorly understood. Objective: Our aim was to identify novel lymphangiogenic genes by identifying lymphangiogenic lung tumor cell lines, and then to use microarray data to generate a "lymphangiogenic" gene signature. METHODS: Tumors from 13 lung tumor cell lines were stained with antibodies against LYVE-1 and Podoplanin. Lymphatic vessels were counted in 5 representative 20X fields per tumor. Average lymphatic vessel densities were then calculated. Cell lines were grouped into lymphangiogenic, non-lymphangiogenic, and intermediate categories. Microarray data from the two extreme groups were then compared to generate a "lymphangiogenic" signature. RESULTS: Four cell lines, (Calu-1, H1993, HCC461, and HCC827) displayed high intratumoral lymphatic density, and five cell lines (Calu-3, H1155, H1395, H1975, and H2073) displayed no intratumoral lymphatic vessels. The "lymphangiogenic" signature obtained from the microarray data from these groups contained 146 genes, including the lymphatic growth factor VEGF-C. CONCLUSIONS: Our preliminary findings suggest that VEGF-C is an important driver of tumor lymphangiogenesis in NSCLC. The other 145 genes in the signature may also serve novel functions in regulating tumor lymphangiogenesis. Together, the results from this project provide mechanistic insight into the process of tumor lymphangiogenesis and metastasis. We believe that this information will lead to the development of new prognostic or predictive markers and therapeutic strategies to improve the outcome of patients with lung cancer.Item [News](1980-01-02) Wilson, SusanItem 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 [UT Southwestern Medical Center News](2013-10-01) Lyda, Alex