Bio

Clinical Focus


  • Cancer > Gynecologic Cancer
  • Cancer > Radiation Oncology
  • Gynecologic Malignancies
  • Brachytherapy
  • Breast Cancer
  • Radiation Oncology
  • Gastrointestinal Cancer
  • Lung Cancer
  • Lymphoma

Academic Appointments


Professional Education


  • Residency: Washington University Dept of Radiation Oncology (2010) MO
  • Internship: Washington University Barnes Jewish Hospital Internal Medicine Residency (2006) MO
  • Medical Education: Washington University School Of Medicine Registrar (2005) MO
  • Board Certification: Radiation Oncology, American Board of Radiology (2011)

Research & Scholarship

Clinical Trials


  • Novel Serum Markers for Monitoring Response to Anti-Cancer Therapy Recruiting

    The purpose of this study is to measure the levels of serum proteins and other biomarkers in cancer patients and in patients suspected of having cancer. We believe that some of these markers may be useful for confirming the diagnosis or for selecting patients for specific types of cancer therapies. These markers may also help to predict response to therapy, relapse after therapy, and survival after therapy.

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  • Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer Recruiting

    This randomized phase III trial studies short course vaginal cuff brachytherapy to see how well it works compared with standard of care vaginal cuff brachytherapy in treating patients with stage I-II endometrial cancer. Short course vaginal cuff brachytherapy, also known as internal radiation therapy, uses (over a shorter period) radioactive material placed directly into or near a tumor in the upper portion of the vagina to kill tumor cells.

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  • Health and Recovery Program in Increasing Physical Activity Level in Stage IA-IIIA Endometrial Cancer Survivors Not Recruiting

    This randomized phase II trial studies how well a health and recovery program works in increasing physical activity level in stage IA-IIIA endometrial cancer survivors. Health and recovery program which includes exercise counseling, Fitbit tracker, and phone or email/text communication may increase the level of physical activity in endometrial cancer survivors and promote and maintain behavior change at a lower cost.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melissa Usoz, 650-723-8843.

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  • Phase I Pilot Study to Evaluate the Prognostic Value of Perfusion CT for Primary Cervical Cancer Not Recruiting

    The investigators hope to learn whether perfusion CT is a useful way to assess primary cervical tumor microenvironment and whether there is a relationship between pretreatment perfusion CT measurements and primary cervical tumor size, lymph node involvement (as assessed by standard of care pretreatment fludeoxyglucose Positron emission tomography/CT (FDG-PET/CT)), and treatment response (as assessed by standard of care 3-month post-therapy FDG-PET/CT).

    Stanford is currently not accepting patients for this trial. For more information, please contact Melissa Usoz, 650-723-8843.

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  • Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer Not Recruiting

    This phase I trial studies the side effects and the best dose of stereotactic body radiation therapy (SBRT) in treating patients with metastatic or recurrent ovarian cancer or primary peritoneal cancer. SBRT may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

    Stanford is currently not accepting patients for this trial. For more information, please contact Elizabeth A. Kidd, 650-725-2174.

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  • Phone or Email Reminder in Increasing Vaginal Dilator Use in Patients With Gynecologic Cancers Undergoing Brachytherapy Not Recruiting

    This randomized, pilot phase I trial studies whether phone or email reminders increases vaginal dilator use in patients with endometrial, cervical, or vaginal cancers after they undergo brachytherapy. Brachytherapy is a type of internal radiation which uses radioactive material placed directly into or near a tumor to kill tumor cells. A reminder program may help increase use of vaginal dilators and decrease long-term side effects following brachytherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dylann Fujimoto, 650-723-8843.

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  • Tissue and Plasma Biomarkers of Lymph Node Involvement in Cervical Cancer Not Recruiting

    The purpose of this study is to measure the levels of serum proteins and other biomarkers in cervical cancer patients. We believe that some of these markers may be useful in selecting patients for specific types of cancer therapies. These markers may also help to predict response to therapy, relapse after therapy, and survival after therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dylann Fujimoto, 650-723-8843.

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Teaching

2019-20 Courses


Publications

All Publications


  • Validated limited gene predictor for cervical cancer lymph node metastases. Oncotarget Bloomstein, J. D., von Eyben, R., Chan, A., Rankin, E. B., Fregoso, D. R., Wang-Chiang, J., Lee, L., Xie, L., David, S. M., Stehr, H., Esfahani, M. S., Giaccia, A. J., Kidd, E. A. 2020; 11 (24): 2302–9

    Abstract

    PURPOSE: Recognizing the prognostic significance of lymph node (LN) involvement for cervical cancer, we aimed to identify genes that are differentially expressed in LN+ versus LN- cervical cancer and to potentially create a validated predictive gene signature for LN involvement.MATERIALS AND METHODS: Primary tumor biopsies were collected from 74 cervical cancer patients. RNA was extracted and RNA sequencing was performed. The samples were divided by institution into a training set (n = 57) and a testing set (n = 17). Differentially expressed genes were identified among the training cohort and used to train a Random Forest classifier.RESULTS: 22 genes showed > 1.5 fold difference in expression between the LN+ and LN- groups. Using forward selection 5 genes were identified and, based on the clinical knowledge of these genes and testing of the different combinations, a 2-gene Random Forest model of BIRC3 and CD300LG was developed. The classification accuracy of lymph node (LN) status on the test set was 88.2%, with an Area under the Receiver Operating Characteristic curve (ROC-AUC) of 98.6%.CONCLUSIONS: We identified a 2 gene Random Forest model of BIRC3 and CD300LG that predicted lymph node involvement in a validation cohort. This validated model, following testing in additional cohorts, could be used to create a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tool that would be useful for helping to identify patients with LN involvement in resource-limited settings.

    View details for DOI 10.18632/oncotarget.27632

    View details for PubMedID 32595829

  • Intensity modulated Ir-192 brachytherapy using high-Z 3D printed applicators. Physics in medicine and biology Skinner, L. B., Niedermayr, T., Prionas, N., Perl, J., Fahimian, B. P., Kidd, E. 2020

    Abstract

    Gynecologic cancers are often asymmetric, yet current Ir-192 brachytherapy techniques provide only limited radial modulation of the dose. The shielded solutions investigated here solve this by providing the ability to modulate between highly asymmetric and radially symmetric dose distributions at a given location. To find applicator designs that can modulate between full dose and less than 50% dose, at the dimensions of the urethra, a 2D calculation algorithm was developed to narrow down the search space. Two shielding design types were then further investigated using Monte Carlo and Boltzmann-solver dose calculation algorithms. 3D printing techniques using ISO10993 certified biocompatible plastics and 3D printable tungsten-loaded plastics were tested. It was also found that shadowing effects set by the shape of the shielding cannot be easily modulated out, hence careful design is required. The shielded applicator designs investigated here, allow for reduction of the dose by over 50% at 5 mm from the applicator surface in desired regions, while also allowing radially symmetric dose with isodose line (IDL) deviations less than 0.5 mm from circular. The shielding designs were also chosen with treatment delivery time in mind. Treatment times for these shielded designs were found to be less than 1.4 times longer than a six-channel unshielded cylinder for the equivalent fully symmetric dose distribution. The 2D calculation methods developed here provide a simple way to rapidly evaluate shielding designs, while the 3D printing techniques also allow for devices with novel shapes to be rapidly prototyped. Both TOPAS Monte Carlo and Acuros BV calculations show that significant dose shaping, and organ at risk (OAR) sparing can be achieved without significantly compromising the plan in regions that require the full dose.

    View details for DOI 10.1088/1361-6560/ab9b54

    View details for PubMedID 32521512

  • Executive summary of the American Radium Society Appropriate Use Criteria for management of uterine carcinosarcoma. Gynecologic oncology Elshaikh, M. A., Modh, A., Jhingran, A., Biagioli, M. C., Coleman, R. L., Gaffney, D. K., Harkenrider, M. M., Heskett, K., Jolly, S., Kidd, E., Lee, L. J., Li, L., Portelance, L., Sherertz, T., Venkatessan, A. M., Wahl, A. O., Yashar, C. M., Small, W. J. 2020

    Abstract

    OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed.METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS.RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival.CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.

    View details for DOI 10.1016/j.ygyno.2020.04.683

    View details for PubMedID 32475772

  • Parametric Response Mapping of Co-registered Positron Emission Tomography and Dynamic Contrast Enhanced Computed Tomography to Identify Radio-resistant Sub-volumes in Locally Advanced Cervical Cancer. International journal of radiation oncology, biology, physics Capaldi, D. P., Hristov, D. H., Kidd, E. A. 2020

    Abstract

    PURPOSE: To identify sub-volumes that may predict treatment response to definitive concurrent chemoradiation therapy (CCRT) using parametric-response-mapping (PRM) of co-registered positron-emission-tomography (PET) and dynamic-contrast-enhanced (DCE) computed-tomography (CT) in locally advanced cervical carcinoma.METHODS AND MATERIALS: Pre- and mid-treatment (after 23±4days of CCRT) DCE CT and PET imaging were performed on 21 cervical cancer patients who were enrolled in a pilot study to evaluate the prognostic-value of CT perfusion for primary cervical cancer (NCT01805141). Three-dimensional co-registered maps of PET/CT standardized-uptake-value (SUV) and DCE CT blood-flow (BF) were generated. PRM was performed using voxel-wise joint histogram analysis to classify voxels within the tumor as highly-metabolic and perfused (SUVhiBFhi), highly-metabolic and hypoxic (SUVhiBFlo), low-metabolically active and hypoxic (SUVloBFlo), or low-metabolically active and perfused (SUVloBFhi) tissue based on thresholds determined from population means of pre-treatment PET SUV and DCE CT BF. Relationships between baseline pre-treatment imaging metrics and relative changes in metabolic-tumor-volume (DeltaMTV), calculated from pre- and during-treatment imaging, were determined using univariable and multivariable linear regression models.RESULTS: The relative volume of three PRM sub-volumes significantly changed during treatment (SUVhiBFhi: p=.04; SUVhiBFlo: p=.0008; SUVloBFhi: p=.02), while SUVloBFlo did not (p=.9). Pre-treatment PET SUVmax (r=-.58,p=.006), PET SUVmean (rho=-.59,p=.005), DCE CT BFmean (r=-.50,p=.02), tumor-volume (rho=-.65,p=.001) and PRM SUVhiBFhi (rho=-.59,p=.004) were negatively correlated with DeltaMTV, while PRM SUVloBFlo was positively-related with DeltaMTV (r=.77,p<.0001). In a multivariable model that predicted DeltaMTV, PRM SUVloBFlo, which combines both PET/CT and DCE CT, was the only significant variable (beta=1.825,p=.03), over both imaging modalities independently.CONCLUSIONS: PRM was applied in locally advanced cervical carcinoma treated definitively with chemoradiation and radioresistant sub-volumes were identified which correlated with changes in MTV and predict treatment-response. Identification of these sub-volumes may assist in clinical decision-making to tailor therapies, such as brachytherapy, in an effort to improve patient outcomes.

    View details for DOI 10.1016/j.ijrobp.2020.03.023

    View details for PubMedID 32251757

  • Sentinel Lymph Node Biopsies in Endometrial Cancer: Practice Patterns among Gynecologic Oncologists in the United States JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY Renz, M., Diver, E., English, D., Kidd, E., Dorigo, O., Karam, A. 2020; 27 (2): 482–88
  • Improving gynecologic brachytherapy patient experience by optimizing MRI, anesthesia, and scheduling to decrease the length of time tandem and ovoid applicators are in place. Brachytherapy Usoz, M., von Eyben, R., Fujimoto, D. K., Kidd, E. A. 2020

    Abstract

    PURPOSE: Brachytherapy requires multiple different steps and plays a critical role in treatment for gynecological cancer. In an effort to improve gynecologic patient experience, we investigated how different aspects of the procedure influence how long the patient has the brachytherapy applicator in place.METHODS AND MATERIALS: We prospectively recorded 145 consecutive tandem and ovoid treatments for 33 patients and determined how anesthesia vs. conscious sedation, MRI or not, and the number of procedures in the day impact applicator in time. The data were analyzed in a mixed effects linear regression model to account for the within-patient correlation.RESULTS: We found average applicator in place time was 179minutes (range: 87-311minutes). Patients who received anesthesia had a significant increase in length of applicator in patient time by an average of 42minutes compared with those who received conscious sedation. Undergoing an MRI increased length of applicator in time by an average of 66minutes, although the actual MRI performed generally took less than 30minutes. Having three or more procedures scheduled for 1day increased the length of time the tandem and ovoid was inserted by an average of 35minutes.CONCLUSION: The use of anesthesia vs. conscious sedation, MRI scans for treatment planning, and number of procedures scheduled per day have significant influence on the duration of brachytherapy treatments. This information can help us work to optimize scheduling and thereby improve patient brachytherapy experience.

    View details for DOI 10.1016/j.brachy.2019.11.011

    View details for PubMedID 31980387

  • Benefit of Cisplatin With Definitive Radiotherapy in Older Women With Cervical Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Xiang, M., Kidd, E. A. 2019; 17 (8): 969-+

    Abstract

    Cisplatin with definitive radiotherapy (RT) is considered the standard of care for cervical cancer; however, older women are frequently undertreated and have worse outcomes compared with younger patients. Because women aged ≥65 years have been disproportionately underrepresented in clinical trials, uncertainties exist regarding how much they benefit from the addition of cisplatin to RT.Women aged ≥65 years with nonmetastatic cervical cancer treated with definitive external-beam RT and brachytherapy were identified in the SEER-Medicare database. Death attributable to cervical cancer (cancer-specific mortality [CSM]) was evaluated against competing risks of death using Gray's test. Propensity score analysis and the Fine-Gray multivariable regression model were used to adjust for baseline differences, including comorbidity.The total cohort comprised 826 patients, of whom 531 (64%) received cisplatin, 233 (28%) were FIGO stage I, 374 (45%) were stage II, and 219 (27%) were stage III-IVA. Older age and chronic kidney disease significantly predicted omission of cisplatin. Virtually all cisplatin dosing was weekly, with a median of 5 cycles. Death from cervical cancer was significantly lower with cisplatin than without (5-year CSM, 31% vs 39%; P=.02; adjusted hazard ratio, 0.72; P=.02), which persisted in propensity score analysis. Receiving ≥5 cycles was required for benefit, as no difference in CSM was seen in patients receiving 1 to 4 cycles versus no cisplatin. Subgroup analyses revealed that the benefit of cisplatin persisted in women aged ≥75 years and those with early-stage disease. Incidence of cytopenia, nausea/vomiting, and hypovolemia increased in patients treated with cisplatin.Administration of cisplatin with definitive RT in women aged ≥65 years was associated with a significant benefit in the incidence of death attributable to cervical cancer, despite competing risks for mortality in an older population. Receiving at least 5 cycles of weekly cisplatin was required for benefit.

    View details for DOI 10.6004/jnccn.2019.7289

    View details for Web of Science ID 000487240600011

    View details for PubMedID 31390586

  • Defining the survival benefit of adjuvant pelvic radiotherapy and chemotherapy versus chemotherapy alone in stages III-IVA endometrial carcinoma. Gynecologic oncology Xiang, M., English, D. P., Kidd, E. A. 2019

    Abstract

    OBJECTIVES: To determine which patients with locoregionally advanced endometrial cancer may benefit from pelvic external beam radiotherapy (EBRT) in addition to chemotherapy compared to chemotherapy alone.METHODS: Patients with FIGO stages III-IVA endometrial carcinoma between 2004 and 2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of pelvic EBRT, analyzed using the Kaplan-Meier method and Cox multivariable regression.RESULTS: In total, 13,270 patients were identified (62% pure endometrioid, 38% serous/clear cell or mixed histology; 22.6% stage IIIA, 4.7% stage IIIB, 71.2% stage IIIC, 1.5% stage IVA), of whom 40% received pelvic EBRT. In univariable analysis, EBRT was associated with absolute 5-year survival increases of 5% and 9% in the endometrioid and non-endometrioid cohorts, respectively (P < 0.0001). In multivariable analyses stratified by stage and histology, patients with a significant benefit from EBRT were stage IIIC (specifically IIIC2) endometrioid (adjusted hazard ratio [HR] 0.73, P = 0.01) and stages IIIB and IIIC non-endometrioid (adjusted HR 0.52, P = 0.01 and adjusted HR 0.79, P < 0.0001). The benefit of EBRT in node-positive patients persisted in those who underwent more extensive lymphadenectomy.CONCLUSIONS: Stages III-IVA endometrial cancer comprised a heterogeneous population with respect to the added benefit of radiotherapy compared to chemotherapy alone. Patients with stage IIIC2 endometrioid and stages IIIB-C non-endometrioid cancer may be most likely to benefit from pelvic EBRT.

    View details for DOI 10.1016/j.ygyno.2019.06.020

    View details for PubMedID 31257010

  • Definitive Radiotherapy with or Without Cisplatin for Cervical Cancer in Older Women Xiang, M., Kidd, E. ELSEVIER SCIENCE INC. 2019: E11
  • Intensity Modulated Radiation Therapy and Image-Guided Adapted Brachytherapy for Cervix Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lin, A. J., Kidd, E., Dehdashti, F., Siegel, B. A., Mutic, S., Thaker, P. H., Massad, L. S., Powell, M. A., Mutch, D. G., Markovina, S., Schwarz, J., Grigsby, P. W. 2019; 103 (5): 1088–97
  • National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma GYNECOLOGIC ONCOLOGY Xiang, M., English, D. P., Kidd, E. A. 2019; 152 (3): 599–604
  • Prognostic Significance of P16 Expression and P53 Expression in Primary Vaginal Cancer. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Nwachukwu, C. R., Harris, J. P., Chin, A., Von Eyben, R., Giaretta, S., Shaffer, J. L., Hiniker, S. M., Kapp, D. S., Folkins, A. K., Kidd, E. A. 2019; 38 (6): 588–96

    Abstract

    To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66 mo [95% confidence interval (CI), 31-96], 34 mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31 mo, P=0.02 and 35 vs 16 mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.

    View details for DOI 10.1097/PGP.0000000000000568

    View details for PubMedID 31593028

  • Survival benefit of radiation in high-risk, early-stage endometrioid carcinoma. Journal of gynecologic oncology Xiang, M., Kidd, E. A. 2019

    Abstract

    To better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations.Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray's test and Fine-Gray regression.In total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1-2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM.High-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3.

    View details for DOI 10.3802/jgo.2020.31.e39

    View details for PubMedID 31912686

  • Improving brachytherapy efficiency with dedicated dosimetrist planners BRACHYTHERAPY Fujimoto, D. K., von Eyben, R., Usoz, M., Kidd, E. A. 2019; 18 (1): 103–7
  • Sentinel lymph node biopsies in endometrial cancer - practice patterns among Gynecologic Oncologists in the United States. Journal of minimally invasive gynecology Renz, M., Diver, E., English, D., Kidd, E., Dorigo, O., Karam, A. 2019

    Abstract

    To evaluate practice patterns among gynecologic oncologists with regards to sentinel lymph node injection and biopsy in endometrial cancer.Observational study with no control group.Active members of the Society of Gynecologic Oncology.After IRB approval, we performed an online survey amongst active members of the Society of Gynecologic Oncology. Members were contacted via email and their answers anonymously captured. Study data were collected using REDCap.318 of 1216 listed members completed the online survey, The majority of respondents (82.7%) perform sentinel lymph node sampling for endometrial cancer staging. Most technical aspects of sentinel lymph node sampling were consistently applied by the vast majority of respondents, including the choice of indocyanine green (ICG) as lymphatic tracer (97.3%) and its injection into the cervix (100%). Other technical aspects of sentinel lymph node sampling, such as the depth of injection, varied amongst respondents. While 50.9% of the respondents perform an intraoperative assessment of the uterus by frozen section, only 17.9% assess sentinel lymph nodes by frozen section and/or touch prep. Some of the respondents' approaches are based on limited data, including (i) the use of sentinel lymph node injection and biopsy for high-risk histologies (performed by 69 - 75% of the respondents dependent upon the histology), (ii) omitting side-specific completion lymphadenectomy in the absence of sentinel node mapping (in up to 57.8%) or (iii) when lymph node metastases are present (in 39.9%).In summary, despite the growing use of sentinel lymph node injection and biopsy in endometrial cancer, practice patterns vary considerably among providers sampled by this survey. Some of the decisions are based on limited evidence and, in some instances, deviate from current published guidelines.

    View details for PubMedID 30980995

  • National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma. Gynecologic oncology Xiang, M., English, D. P., Kidd, E. A. 2018

    Abstract

    OBJECTIVES: To investigate outcomes of adjuvant therapy for serous and clear cell endometrial carcinoma, as prior studies are limited by sample size and/or patient heterogeneity. National guidelines permit substantial variations in treatment, suggesting the need for additional data.METHODS: Patients with FIGO stages I-III serous or clear cell uterine carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant external beam radiation, brachytherapy, and chemotherapy were determined using SEER fields and Medicare claims. The primary outcome was death from endometrial cancer (cancer-specific mortality [CSM]) evaluated using Gray's test (univariable analysis, UVA) and Fine-Gray regression (multivariable analysis, MVA).RESULTS: A total of 1789 patients (1437 serous, 352 clear cell) were identified. In stages I-II patients (n = 1188), brachytherapy was significant for survival in UVA (P = 0.03) and MVA (P = 0.02). Additionally, in the subset with serous histology (n = 947), chemotherapy was also significant in UVA (P = 0.002) and approached significance in MVA (P = 0.05). The 4-year CSM for stages I-II serous cancers was 25% without brachytherapy or chemotherapy, 15% with one, and 9% with both (P ≤ 0.05 for all pairwise comparisons). In stage III patients (n = 601), chemotherapy was significant in UVA (P = 0.002) and MVA (P = 0.006). Most (81%) patients underwent lymph node dissection, which predicted lower CSM in stage III (P = 0.001) but not stages I-II patients.CONCLUSIONS: Our results suggest brachytherapy benefits stages I-II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I-II serous cancers.

    View details for PubMedID 30551884

  • Prognostic Significance of P16 Expression and P53 Expression in Primary Vaginal Cancer. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Nwachukwu, C. R., Harris, J. P., Chin, A., Von Eyben, R., Giaretta, S., Shaffer, J. L., Hiniker, S. M., Kapp, D. S., Folkins, A. K., Kidd, E. A. 2018

    Abstract

    To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66mo [95% confidence interval (CI), 31-96], 34mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31mo, P=0.02 and 35 vs 16mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.

    View details for PubMedID 30516621

  • IMRT and image-guided adapted brachytherapy for cervix cancer. International journal of radiation oncology, biology, physics Lin, A. J., Kidd, E., Dehdashti, F., Siegel, B. A., Mutic, S., Thaker, P. H., Massad, L. S., Powell, M. A., Mutch, D. G., Markovina, S., Schwarz, J., Grigsby, P. W. 2018

    Abstract

    PURPOSE: To report long-term outcomes of cervical cancer patients treated with intensity-modulated radiation therapy and 3D image-guided adapted brachytherapy (IMRT/3D-IGABT) compared to 2D external irradiation and 2D brachytherapy (2D EBRT/BT).METHODS AND MATERIALS: This study included patients with newly diagnosed cervical cancer and pre-treatment FDG-PET treated with curative-intent irradiation from 1997-2013. Treatment policy changed from 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer specific survival (CSS), and overall survival (OS) were evaluated. Late GI and GU toxicity was scored with Common Terminology Criteria for Adverse Events.RESULTS: Median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n=300) was 15.3 years (10.8-20.5) and in the IMRT/3D-IGABT group (n=300) 7 years (5-12.4). Tumors were FIGO stage IB1-IB2 (33%), IIA-IIB (41%), and IIIA-IVA (26%). The 5-year freedom from recurrence (FFR), CSS, and OS for 2D EBRT/BT patients was 57% FFR, 62% CSS, and 57% OS. For IMRT/3D-IGABT, the 5-year results were 65% FFR (p=0.04), 69% CSS (p=0.01), and 61% OS (p=0.04). When stratified by PET lymph node status, disease control was most improved with IMRT/3D-IGABT vs. 2D EBRT/BT in patients with positive pelvic lymph nodes only (p=0.02). Cumulatively, there were 88 (15%) grade ≥3 late bowel/bladder toxicity (2D EBRT/BT: 55 (18%) vs. IMRT/3D-IGABT: 33 (11%), p=0.02).CONCLUSIONS: IMRT/3D-IGABT was associated with improved survival and decreased GI and GU toxicity in cervical cancer patients compared to 2D EBRT/BT.

    View details for PubMedID 30445171

  • Improving brachytherapy efficiency with dedicated dosimetrist planners. Brachytherapy Fujimoto, D. K., von Eyben, R., Usoz, M., Kidd, E. A. 2018

    Abstract

    PURPOSE: To investigate the different factors affecting the procedure duration for high-dose-rate brachytherapy for gynecologic malignancies.METHODS AND MATERIALS: We prospectively recorded 86 consecutive vaginal cylinder (VC) treatments and 82 tandem and ovoid treatments. Key time points in the brachytherapy process, identity of the planner and checker, number of treatments per day, and fraction number per patient were recorded. The data were analyzed in a mixed effects linear regression model to account for the within patient correlation. Post hoc pair-wise comparisons were performed using a Dunnett's adjustment for comparisons to a single control group and using a Tukey adjustment for all pair-wise comparisons.RESULTS: We focused on several key time intervals in the treatment: total, nursing/anesthesia preprocedure, procedure, contouring, and planning times. In analysis, multiple factors significantly influenced VC timing but not tandem and ovoid timing. The planners were separated and analyzed based on experience and profession. Inexperienced physicists planning times were on average 18min (p=0.0010) and 14min (p=0.0038) slower than dedicated brachytherapy dosimetrist and experienced physicists, respectively. An increase in the number of procedures for the day of treatment increased the VC total time (p=0.0218). The VC procedure time changed depending on whether it was the patients' first, second, or third VC treatment (p<0.0001).CONCLUSIONS: The use of dosimetrists as dedicated planners for brachytherapy is more cost and time efficient. There are multiple variables affecting brachytherapy treatment with actionable opportunities to improve procedure scheduling.

    View details for PubMedID 30391061

  • Pilot study of combined FDG-PET and dynamic contrast-enhanced CT of locally advanced cervical carcinoma before and during concurrent chemoradiotherapy suggests association between changes in tumor blood volume and treatment response CANCER MEDICINE Banks, T. I., von Eyben, R., Hristov, D., Kidd, E. A. 2018; 7 (8): 3642–51

    View details for DOI 10.1002/cam4.1632

    View details for Web of Science ID 000441430100011

  • Pilot study of combined FDG-PET and dynamic contrast-enhanced CT of locally advanced cervical carcinoma before and during concurrent chemoradiotherapy suggests association between changes in tumor blood volume and treatment response. Cancer medicine Banks, T. I., von Eyben, R., Hristov, D., Kidd, E. A. 2018

    Abstract

    Modern PET/CT radiotherapy simulators offer FDG-PET and dynamic contrast-enhanced (DCE) CT imaging for combined volumetric assessment of tumor metabolism and perfusion. However, the clinical utility of such assessment has not been clearly defined. Thus, in a prospective longitudinal study of primary cervical tumors treated with concurrent chemoradiotherapy (CCRT) we evaluated: (1) whether PET and perfusion parameters correlate or provide complementary information; (2) what imaging changes occur during CCRT; and (3) whether any parameters are predictive of treatment response as assessed by PET/CT 3months posttherapy. FDG-PET/CT and DCE-CT scans were performed on 21 patients prior to and during CCRT. Coregistered volumetric parametric maps of standardized uptake value (SUV) measures and perfusion parameters blood flow (BF), blood volume (BV), and permeability were generated. Summary statistics for these parameters and their changes were calculated within the metabolic tumor volume (MTV). Correlations between SUV and BF/BV/permeability on local and global bases were assessed with Pearson's coefficient r. MTV, maximum SUV, and mean SUV decreased significantly between the pre- and during-treatment time points, while mean BV and permeability increased significantly. Global correlations between mean BF/BV/permeability and mean SUV values (-.15

    View details for PubMedID 29963760

  • Rate of Change in Quantitative PET/CT Metrics Prior to Definitive Chemoradiotherapy for Cervical Cancer Does not Add Prognostic Information Over Single Time Point Metrics Prionas, N. D., von Eyben, R., Hristov, D., Kidd, E. ELSEVIER SCIENCE INC. 2018: E31–E32
  • Radiation therapy improves disease-specific survival in women with Stage II endometrioid endometrial cancer-Brachytherapy may be sufficient BRACHYTHERAPY Nwachukwu, C. R., Von-Eyben, R., Kidd, E. A. 2018; 17 (2): 383–91

    Abstract

    To evaluate disease-specific survival (DSS) outcomes in Stage II endometrioid endometrial cancer (EC) patients based on pathology and treatment information including adjuvant radiotherapy and lymph node assessment.Using the Surveillance, Epidemiology, and End Results database, 2877 patients with Stage II EC diagnosed between 2004 and 2012 treated with radiation were identified. DSS was determined for different modalities of radiation. Kaplan-Meier estimates of survival and Cox regression modeling were used to explore the risk associated with various factors on DSS.The 4-year DSS for the study population was 90%. Radiation was associated with improved 4-year DSS when compared to no radiotherapy (p = 0.03). Patients with Grade 2 and 3 tumors had improved 4-year DSS with radiation (94% vs. 90%, p = 0.02 and 81% vs. 73%, p = 0.15), respectively, but no differences in DSS when vaginal brachytherapy alone was compared with external beam alone or both. Patients with Grade 2 (p = 0.002) and Grade 3 (p < 0.001) tumors without a lymph node dissection (LND) had worse DSS compared to patients with any LND. Patients with Grade 3 tumors without an LND who received radiation showed improved DSS (p = 0.008). Multivariable analysis revealed that age >60 years (p < 0.001), Grade 3 (p < 0.001), no radiotherapy (p = 0.05), and no LNDs (p < 0.001) were significant prognostic factors for worse DSS.Adjuvant radiation, whether delivered by brachytherapy or external beam radiation, is associated with improved DSS in Stage II EC patients with high-grade tumors, therefore brachytherapy may be sufficient.

    View details for PubMedID 29198879

  • Less than whole uterus irradiation for locally advanced cervical cancer maintains locoregional control and decreases radiation dose to bowel. Practical radiation oncology Kozak, M. M., Koenig, J. L., von Eyben, R., Kidd, E. A. 2018

    Abstract

    To evaluate whether our institutional standard of less than whole uterus (LTWU) irradiation affects locoregional control in patients with locally advanced cervical cancer.We retrospectively reviewed 53 patients with stage IB-IVB cervical carcinoma treated with image-guided IMRT and brachytherapy. The entire uterus was not included in the clinical target volume (CTV), as is our institutional standard. Dosimetric parameters were obtained, including: GTV PET tumor volume, uterus volume excluding GTV, proportion of uterus included in the planning target volume (PTV, %), volume of overlap between uterus and prescription dose (cc), minimum and mean dose to the uterus, and bowel V40 and D200cc. Local, regional, and distant failure, and death were recorded.The median proportion of the uterus included in the PTV was 66%. With a median follow-up of 44 months, no patient experienced isolated local recurrence and 2-year locoregional failure was 10.9%. GTV PET tumor volume correlated significantly with increased chance of any failure (p=0.049; 95% CI, 1.000-1.018). Compared to patients who had ≥90% of the uterus included in the PTV (n=12), those who had <90% (n=41) of the uterus included in the PTV had significantly lower bowel V40 (p=0.049) and D200cc (p=0.006).LTWU irradiation for locally advanced cervical cancer does not compromise locoregional control and reduces bowel V40 and D200cc. Further investigation is required to evaluate whether this reduction in bowel dose translates to a clinically significant reduction in bowel toxicity and whether modifications should be made to recommended definitive cervix IMRT volumes.

    View details for DOI 10.1016/j.prro.2018.10.009

    View details for PubMedID 30395974

  • Extent of lymphovascular space invasion may predict lymph node metastasis in uterine serous carcinoma GYNECOLOGIC ONCOLOGY Qian, Y., Pollom, E. L., Nwachukwu, C., Seiger, K., von Eyben, R., Folkins, A. K., Kidd, E. A. 2017; 147 (1): 24–29

    Abstract

    Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC.Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed.88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04).Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma.

    View details for PubMedID 28709703

    View details for PubMedCentralID PMC5605436

  • Consideration of patient and disease characteristics in selecting radiation regimens for treatment of bone metastases. Practical radiation oncology Liu, Y., von Eyben, R., Kidd, E. A. 2017

    Abstract

    Radiation therapy is one of the mainstays of treatment for painful bone metastases; however, the optimal fractionation and dosing of radiation for a given patient and disease characteristics are still subject to debate.We retrospectively examined 475 patients who received radiation for bone metastases at our institution from 2009 through 2014 and evaluated survival outcomes based on parameters of their first treatment course and patient demographics. Kaplan-Meier analysis was used to analyze factors associated with overall survival (OS). A recursive partition analysis (RPA) was used to generate a decision tree of patient characteristics resulting in significant differences in survival. A Cox model was used to verify the RPA and evaluate the significance of biologically equivalent dose (BED) along with other factors.In our cohort, median age was 62 years and median Karnofsky performance status (KPS) was 70. Survival time by primary tumor type: breast (median, 35.9 months), prostate (12.8 months), other (median, 11.0 months), lung (median, 5.3 months), and gastrointestinal (median, 4.0 months) (P < .0001). Primary tumor type and KPS significantly affected survival, whereas age was also significant for survival in certain primary tumor types. Pain control was not found to be significantly affected by primary tumor type (P = .72) or BED (P = .14).Our data demonstrate that selection of radiation fractionation schedules should take into account primary tumor type, KPS, and age, and we have generated an RPA model including these factors to help guide decision making. We also found that shorter fractionation schedules are as effective as longer fractionation schedules for pain control, regardless of primary tumor type.

    View details for DOI 10.1016/j.prro.2017.06.008

    View details for PubMedID 28751228

  • ACR Appropriateness Criteria (R) Management of Recurrent Endometrial Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Elshaikh, M. A., Vance, S., Gaffney, D. K., Biagioli, M., Jhingran, A., Jolly, S., Kidd, E., Lee, L. J., Ll, L., Moore, D. H., Rao, G. G., Wahl, A. O., Williams, N. L., Yashar, C. M., Small, W. 2016; 39 (5): 507-515

    Abstract

    In women with endometrial carcinoma (EC), tumor recurrences tend to occur in the 2- to 3-year period following surgical staging. Management of disease recurrence in EC poses significant challenges. These patients represent a heterogenous group where histologic subtypes, previous adjuvant management, interval since completion of adjuvant therapy, and size and site(s) of disease recurrence all have important implications on salvage therapies and prognosis. No randomized controlled trials have been published to determine optimal management in this group of patients. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.Five clinical variants were developed to address common scenarios in the management of women with recurrent EC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings.In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with recurrent EC.

    View details for DOI 10.1097/COC.0000000000000318

    View details for PubMedID 27400117

  • Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline. Journal of global oncology Chuang, L. T., Temin, S., Camacho, R., Duenas-Gonzalez, A., Feldman, S., Gultekin, M., Gupta, V., Horton, S., Jacob, G., Kidd, E. A., Lishimpi, K., Nakisige, C., Nam, J., Ngan, H. Y., Small, W., Thomas, G., Berek, J. S. 2016; 2 (5): 311–40

    Abstract

    PURPOSE: To provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer.METHODS: ASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines.RESULTS: Five existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater.RECOMMENDATIONS: Clinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

    View details for DOI 10.1200/JGO.2016.003954

    View details for PubMedID 28717717

  • ACR Appropriateness Criteria (R) Adjuvant Management of Early-Stage Endometrial Cancer ONCOLOGY-NEW YORK Wahl, A. O., Gaffney, D. K., Jhingran, A., Yashar, C. M., Biagioli, M., Elshaikh, M. A., Jolly, S., Kidd, E., Lee, L. J., Li, L., Moore, D. H., Rao, G. G., Williams, N. L., Small, W. 2016; 30 (9): 816-822

    Abstract

    These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

    View details for Web of Science ID 000383414400005

    View details for PubMedID 27633412

  • Nomogram to Predict Risk of Lymph Node Metastases in Patients With Endometrioid Endometrial Cancer. International journal of gynecological pathology Pollom, E. L., Conklin, C. M., von Eyben, R., Folkins, A. K., Kidd, E. A. 2016; 35 (5): 395-401

    Abstract

    Pelvic lymphadenectomy in early-stage endometrial cancer is controversial, but the findings influence prognosis and treatment decisions. Noninvasive tools to identify women at high risk of lymph node metastasis can assist in determining the need for lymph node dissection and adjuvant treatment for patients who do not have a lymph node dissection performed initially. A retrospective review of surgical pathology was conducted for endometrioid endometrial adenocarcinoma at our institution. Univariate and multivariate logistic regression analysis of selected pathologic features were performed. A nomogram to predict for lymph node metastasis was constructed. From August 1996 to October 2013, 296 patients underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy for endometrioid endometrial adenocarcinoma. Median age at surgery was 62.7 yr (range, 24.9-93.6 yr). Median number of lymph nodes removed was 13 (range, 1-72). Of all patients, 38 (12.8%) had lymph node metastases. On univariate analysis, tumor size ≥4 cm, grade, lymphovascular space involvement, cervical stromal involvement, adnexal or serosal or parametrial involvement, positive pelvic washings, and deep (more than one half) myometrial invasion were all significantly associated with lymph node involvement. In a multivariate model, lymphovascular space involvement, deep myometrial invasion, and cervical stromal involvement remained significant predictors of nodal involvement, whereas tumor size of ≥4 cm was borderline significant. A lymph node predictive nomogram was constructed using these factors. Our nomogram can help estimate risk of nodal disease and aid in directing the need for additional surgery or adjuvant therapy in patients without lymph node surgery. Lymphovascular space involvement is the most important predictor for lymph node metastases, regardless of grade, and should be consistently assessed.

    View details for DOI 10.1097/PGP.0000000000000246

    View details for PubMedID 26598977

  • ACR Appropriateness Criteria (R) Adjuvant Therapy in Vulvar Cancer ONCOLOGY-NEW YORK Jolly, S., Soni, P., Gaffney, D. K., Biagioli, M., Elshaikh, M. A., Jhingran, A., Kidd, E., Lee, L. J., Li, L., Moore, D. H., Rao, G. G., Wahl, A. O., Williams, N. L., Yashar, C. M., Small, W. 2015; 29 (11): 867-?

    Abstract

    These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy.

    View details for Web of Science ID 000365147100011

    View details for PubMedID 26568534

  • 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 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Xie, W., Wu, X., Xue, R., Lin, X., Kidd, E. A., Yan, S., Zhang, Y., Zhai, T., Lu, J., Wu, L., Zhang, H., Huang, H., Chen, Z., Li, D., Xie, L. 2015; 91 (1): 206-212

    Abstract

    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).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.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.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.

    View details for DOI 10.1016/j.ijrobp.2014.09.009

    View details for Web of Science ID 000346415500028

  • 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. International journal of radiation oncology, biology, physics Xie, W., Wu, X., Xue, R., Lin, X., Kidd, E. A., Yan, S., Zhang, Y., Zhai, T., Lu, J., Wu, L., Zhang, H., Huang, H., Chen, Z., Li, D., Xie, L. 2015; 91 (1): 206-212

    Abstract

    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).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.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.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.

    View details for DOI 10.1016/j.ijrobp.2014.09.009

    View details for PubMedID 25442332

  • ACR Appropriateness Criteria® Advanced Stage Endometrial Cancer. American journal of clinical oncology Elshaikh, M. A., Yashar, C. M., Wolfson, A. H., Cardenes, H. R., Erickson, B., Jhingran, A., Jolly, S., Kidd, E., Lee, L. J., Mayr, N. A., Moore, D., Rao, G. G., Small, W., Varia, M. A., Wahl, A. O., Yuh, W., Gaffney, D. K. 2014; 37 (4): 391-396

    Abstract

    Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Four clinical variants were developed to address common scenarios in the management of women with advanced-stage endometrial carcinoma. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings.In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with advanced-stage endometrial carcinoma.

    View details for DOI 10.1097/COC.0000000000000098

    View details for PubMedID 24977691

  • Impact of socioeconomic status and ethnic enclave on cervical cancer incidence among Hispanics and Asians in California. Gynecologic oncology Froment, M., Gomez, S. L., Roux, A., DeRouen, M. C., Kidd, E. A. 2014; 133 (3): 409-415

    Abstract

    This study aimed to evaluate the incidence of cervical cancer by nativity [United States (US) versus non-US], neighborhood socioeconomic status and ethnic enclave among Hispanics and Asians in California.Using data from the California Cancer Registry, information on all primary invasive cervical cancer (Cca) patients diagnosed in California from January 1, 1990 through December 31, 2004 was obtained. We analyzed the influence of enclave, socioeconomic status and nativity on Cca incidence.Among the 22,189 Cca cases diagnosed between 1990 and 2004, 50% were non-Hispanic white, 39% Hispanic and 11% Asian women, and 63% US-born. Seventy percent of the Cca cases were squamous cell carcinoma, 19% adenocarcinoma and 11% other histologies. Higher incidence of Cca was observed in high enclave (76%) and low socioeconomic status (70%) neighborhoods. By ethnic group, US-born women showed lower rates of squamous cell carcinoma compared to foreign-born women. Hispanics living in low socioeconomic and high enclave had 12.7 times higher rate of Cca than those living in high socioeconomic, low enclave neighborhoods. For Asian women incidence rates were 6 times higher in the low socioeconomic, high enclave neighborhoods compared to those living in high socioeconomic, low enclave neighborhoods.More targeted outreach to increase Pap smear screening and human papilloma virus vaccination for women living in high enclave neighborhoods can help decrease the incidence of Cca in these groups of women.

    View details for DOI 10.1016/j.ygyno.2014.03.559

    View details for PubMedID 24674831

  • Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modulated radiation therapy. International journal of radiation oncology, biology, physics Bazan, J. G., Luxton, G., Kozak, M. M., Anderson, E. M., Hancock, S. L., Kapp, D. S., Kidd, E. A., Koong, A. C., Chang, D. T. 2013; 87 (5): 983-991

    Abstract

    To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy.We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters.Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

    View details for DOI 10.1016/j.ijrobp.2013.09.017

    View details for PubMedID 24161422

  • Primary squamous cell carcinoma of the vagina: Prognostic factors, treatment patterns, and outcomes. Gynecologic oncology Hiniker, S. M., Roux, A., Murphy, J. D., Harris, J. P., Tran, P. T., Kapp, D. S., Kidd, E. A. 2013; 131 (2): 380-385

    Abstract

    Primary squamous cell carcinoma (SCCA) of the vagina is a rare malignancy with limited data to guide treatment. We evaluated prognostic factors and outcomes for patients with primary vaginal SCCA treated with definitive radiation therapy at a single institution.A retrospective analysis was performed on patients treated for primary vaginal SCCA from 1959 to 2011.Ninety-one patients with primary vaginal SCCA were treated with definitive radiation therapy. Thirty-eight patients had FIGO stage I, 28 stage II, 13 stage III, and 12 stage IV disease. The mean total dose was 70.1Gy. Two-year overall survival (OS), locoregional control rate (LRC), and distant metastasis-free survival by stage were, respectively: stage I: 96.2%, 80.6%, 87.5%; stage II: 92.3%, 64.7%, 84.6%; stage III: 66.6%, 44.4%, 50.0%; and stage IV: 25.0%, 14.3%, 25.0%. Treatment with total dose over 70Gy was associated with improved OS (p=0.0956) and LRC (p=0.055). There was a significant difference in median dose received by patients who developed grade 3/4 toxicity compared to those who did not (82.9Gy versus 70.0Gy, p=0.0019). None of the 10 patients treated with IMRT experienced locoregional recurrence or grade 3/4 toxicity. Tumor size larger than 4cm was associated with worse OS (p=0.0034) and LRC (p=0.006).Our analysis suggests that the optimal dose for definitive treatment of SCCA of the vagina lies between 70 and 80Gy. Treatment with IMRT may allow for dose escalation with reduced toxicity and excellent LRC. Tumor size over 4cm is associated with inferior outcomes and may require additional treatment modalities.

    View details for DOI 10.1016/j.ygyno.2013.08.012

    View details for PubMedID 23954572

  • ACR APPROPRIATENESS CRITERIA (R) Management of Vaginal Cancer ONCOLOGY-NEW YORK Lee, L. J., Jhingran, A., Kidd, E., Cardenes, H. R., Elshaikh, M. A., Erickson, B., Mayr, N. A., Moore, D., Puthawala, A. A., Rao, G. G., Small, W., Varia, M. A., Wahl, A. O., Wolfson, A. H., Yashar, C. M., Yuh, W., Gaffney, D. K. 2013; 27 (11): 1166-1173

    Abstract

    Due to its rarity, treatment guidelines for vaginal cancer are extrapolated from institutional reports and prospective studies of cervical and anal cancer. An expert panel was convened to reach consensus on the selection of imaging and therapeutic modalities. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by the panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four variants were developed to represent clinical scenarios in vaginal cancer management. Group members reached consensus on the appropriateness of the pretreatment evaluation and therapeutic interventions. This article represents the consensus opinion of an expert panel and may be used to inform clinical recommendations in vaginal cancer management.

    View details for Web of Science ID 000327687900016

  • Treatment approach and outcomes of vaginal melanoma. International journal of gynecological cancer Kirschner, A. N., Kidd, E. A., Dewees, T., Perkins, S. M. 2013; 23 (8): 1484-1489

    Abstract

    To describe the characteristics of primary vaginal melanoma patients in the Surveillance, Epidemiology, and End Result database and to determine the outcome from the treatment approaches.From the Surveillance, Epidemiology, and End Result registry, 201 patients with vaginal melanoma were identified. Patients' characteristics and prognostic factors including age, race, extent of surgery, and use of radiation therapy were obtained.The median age was 68 years (range, 28-100 years). The population was 73% white, 11% black, and 16% Asian/American Indian. International Federation of Gynecology and Obstetrics staging results were stage I (46%), stage II (18%), stage III (3%), stage IVA (3%), stage IVB (12%), and unknown (18%). Treatment approach included surgical resection of the primary site in 70%, whereas 35% of the patients underwent lymph node resection. Approximately 40% of the patients received radiotherapy, which was primarily used in the adjuvant setting. Overall survival at 2 and 5 years was 24% and 15%, respectively. Presence of lymph nodes at diagnosis was associated with worse overall survival (hazard ratio, 1.98; P = 0.02). Adjuvant radiation did not offer a statistically significant overall survival advantage compared to surgery alone.Vaginal melanoma is a rare diagnosis primarily affecting the elderly. Overall survival is low even for patients presenting with disease limited to the vagina. Lymph node involvement at diagnosis is strongly predictive of worse overall survival. Most patients are treated with surgical resection with varying use of adjuvant radiotherapy. Further research is needed to identify the etiology and improve the outcome of this aggressive disease.

    View details for DOI 10.1097/IGC.0b013e3182a1ced8

    View details for PubMedID 23945202

  • ACR Appropriateness Criteria® management of locoregionally advanced squamous cell carcinoma of the vulva. American journal of clinical oncology Kidd, E., Moore, D., Varia, M. A., Gaffney, D. K., Elshaikh, M. A., Erickson, B., Jhingran, A., Lee, L. J., Mayr, N. A., Puthawala, A. A., Rao, G. G., Small, W., Wahl, A. O., Wolfson, A. H., Yashar, C. M., Yuh, W., Cardenes, H. R. 2013; 36 (4): 415-422

    Abstract

    Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients.The American College of Radiology Appropriateness Criteria are evidenced-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to formulate recommendations.Three clinical variants were developed to address common scenarios in the management of LRAVC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches, with numerical ratings and descriptive commentary.In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate management of patients with LRAVC.

    View details for DOI 10.1097/COC.0b013e318295af1d

    View details for PubMedID 23872794

  • Impact of socioeconomic status and degree of ethnic isolation on cervical cancer incidence among Hispanics and Asians in California Froment, M., Roux, A., DeRouen, M. C., Gomez, S., Kidd, E. A. AMER SOC CLINICAL ONCOLOGY. 2013
  • Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kidd, E. A., Thomas, M., Siegel, B. A., Dehdashti, F., Grigsby, P. W. 2013; 85 (1): 116-122

    Abstract

    Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUVmax) and the variability of uptake (FDGhetero), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUVmax and FDGhetero during concurrent chemoradiation for cervical cancer and their association with post-treatment response.Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUVmax, FDGhetero, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT.For all patients, the average pretreatment SUVmax was 17.8, MTV was 55.4 cm3, and FDGhetero was -1.33. A similar decline in SUVmax was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDGhetero decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUVmax had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUVmax, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUVmax (P=.037), week 4 FDGhetero (P=.005), pretreatment MTV (P=.008), and pretreatment FDGhetero (P=.008) were all significantly associated with post-treatment PET response.SUVmax shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.

    View details for DOI 10.1016/j.ijrobp.2012.02.056

    View details for PubMedID 22520475

  • FDG-PET-based prognostic nomograms for locally advanced cervical cancer GYNECOLOGIC ONCOLOGY Kidd, E. A., El Naqa, I., Siegel, B. A., Dehdashti, F., Grigsby, P. W. 2012; 127 (1): 136-140

    Abstract

    We previously found several individual FDG/PET-based prognostic factors for cervical cancer, specifically cervical tumor SUVmax, tumor volume, and highest level of lymph node (LN) involvement. For this study, we evaluate the combined use of these three prognostic factors assessed on pretreatment FDG-PET for predicting recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS).The study included 234 cervical cancer patients, FIGO stage Ib1-IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, SUVmax, and LN status were recorded. Using these PET-based factors, prognostic nomograms were created for RFS, DSS, and OS, and their prediction accuracies were measured using the concordance index (c-statistic).Fifty-three percent of patients had FDG-avid LN on PET; the highest level of nodal involvement was pelvic in 84, para-aortic in 41, and supraclavicular in 10. The average cervix tumor SUVmax was 12.4 (range, 2.1-50.4) and PET tumor volume average was 66.4 cm3 (range, 3.0-535.7 cm3). The median follow-up was 40.7 months for patients alive at last follow-up. PET LN status had the greatest influence on outcome. The c-statistics for the 3 nomograms were 0.741 for RFS, 0.739 for DSS, and 0.658 for OS. The PET-based nomograms performed better than FIGO stage with c-statistics of 0.605, 0.600 and 0.559 for RFS, DSS and OS, respectively.Pretreatment FDG-PET LN status, cervical tumor SUVmax, and tumor volume combined in a nomogram create good models for predicting cervical cancer RFS, DSS, and OS.

    View details for DOI 10.1016/j.ygyno.2012.06.027

    View details for Web of Science ID 000308783800026

    View details for PubMedID 22735785

  • ACR Appropriateness Criteria (R) Definitive Therapy for Early-Stage Cervical Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Small, W., Strauss, J. B., Jhingran, A., Yashar, C. M., Cardenes, H. R., Erickson-Wittmann, B. A., Gullett, N., Kidd, E., Lee, L. J., Mayr, N. A., Moore, D., Puthawala, A. A., Rao, G. G., Varia, M. A., Wahl, A. O., Wolfson, A. H., Yuh, W., Gaffney, D. K. 2012; 35 (4): 399-405

    Abstract

    The definitive treatment of early-stage cervical cancer involves multidisciplinary decision making. This expert panel was convened to reach consensus on the selection of appropriate therapies based on patient and disease characteristics at presentation.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or the treatment.Three clinical variants were developed to represent common scenarios in the treatment of early-stage cervical cancer. Group members reached consensus on the appropriateness of therapeutic options. This process yielded numerical ratings and descriptive commentary.This manuscript represents the consensus opinion of an expert panel based on a survey of all available medical literature. This manuscript may be used to inform the clinical decision making of physicians involved in the treatment of early-stage cervical cancer.

    View details for DOI 10.1097/COC.0b013e3182610537

    View details for Web of Science ID 000306599200017

    View details for PubMedID 22810416

  • RADIATION THERAPY FOR PILOCYTIC ASTROCYTOMAS OF CHILDHOOD INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Mansur, D. B., Rubin, J. B., Kidd, E. A., King, A. A., Hollander, A. S., Smyth, M. D., Limbrick, D. D., Park, T. S., Leonard, J. R. 2011; 79 (3): 829-834

    Abstract

    Though radiation therapy is generally considered the most effective treatment for unresectable pilocytic astrocytomas in children, there are few data to support this claim. To examine the efficacy of radiation therapy for pediatric pilocytic astrocytomas, we retrospectively reviewed the experience at our institution.Thirty-five patients 18 years old or younger with unresectable tumors and without evidence of neurofibromatosis have been treated since 1982. Patients were treated with local radiation fields to a median dose of 54 Gy. Six patients were treated with radiosurgery to a median dose of 15.5 Gy. Five patients were treated with initial chemotherapy and irradiated after progression.All patients were alive after a median follow-up of 5.0 years. However, progression-free survival was 68.7%. None of 11 infratentorial tumors progressed compared with 6 of 20 supratentorial tumors. A trend toward improved progression-free survival was seen with radiosurgery (80%) compared with external beam alone (66%), but this difference did not reach statistical significance. Eight of the 9 patients progressing after therapy did so within the irradiated volume.Although the survival of these children is excellent, almost one third of patients have progressive disease after definitive radiotherapy. Improvements in tumor control are needed in this patient population, and the optimal therapy has not been fully defined. Prospective trials comparing initial chemotherapy to radiation therapy are warranted.

    View details for DOI 10.1016/j.ijrobp.2009.11.015

    View details for Web of Science ID 000287382400027

    View details for PubMedID 20421157

  • The Use of Positron Emission Tomographic Imaging for Image-Guided Therapy GYNECOLOGIC RADIATION THERAPY: NOVEL APPROACHES TO IMAGE-GUIDANCE AND MANAGEMENT Kidd, E., Grigsby, P., Viswanathan, A. N., Kirisits, C., Erickson, B. E., Potter, R. 2011: 41–48
  • CLINICAL OUTCOMES OF DEFINITIVE INTENSITY-MODULATED RADIATION THERAPY WITH FLUORODEOXYGLUCOSE-POSITRON EMISSION TOMOGRAPHY SIMULATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kidd, E. A., Siegel, B. A., Dehdashti, F., Rader, J. S., Mutic, S., Mutch, D. G., Powell, M. A., Grigsby, P. W. 2010; 77 (4): 1085-1091

    Abstract

    This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment.This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0.The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351).Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy.

    View details for DOI 10.1016/j.ijrobp.2009.06.041

    View details for Web of Science ID 000279489500018

    View details for PubMedID 19880262

  • Anal cancer maximum F-18 fluorodeoxyglucose uptake on positron emission tomography is correlated with prognosis RADIOTHERAPY AND ONCOLOGY Kidd, E. A., Dehdashti, F., Siegel, B. A., Grigsby, P. W. 2010; 95 (3): 288-291

    Abstract

    To evaluate anal cancer uptake of F-18 fluorodeoxyglucose (FDG) measured as the maximum standardized uptake value (SUV(max)) by positron emission tomography (PET) and its correlation with prognostic factors.The study population consisted of 77 patients with stages 0-IIIB anal cancer who underwent pre-treatment FDG-PET. Tumor histology included 65 squamous cell, 11 basaloid, and 1 small cell cancers. SUV(max) and sites of lymph node metastasis were recorded. We analyzed the association between SUV(max) and prognostic factors.The mean SUV(max) was 10.0 (range 1.0-43.1). The stage distribution included: 2 stage 0, 7 stage I, 49 stage II, 10 stage IIIA, 9 stage IIIB. SUV(max) and clinical tumor size were not associated (R(2)=0.338). Histology did not significantly influence SUV(max) (mean SUV(max) 10.0 for squamous versus 9.90 for basaloid). Higher SUV(max) was associated with an increased risk of nodal metastasis at diagnosis (p<0.0001). Higher SUV(max) was associated with worse disease-free survival (p=0.05). Patients with high anal tumor SUV(max) at diagnosis were at an increased risk of persistent or recurrent disease on post-therapy FDG-PET performed less than 4months after completing therapy (p=0.0402).SUV(max) is a valuable biomarker of anal cancer prognosis, predicting increased risk of lymph node metastasis and worse disease-free survival.

    View details for DOI 10.1016/j.radonc.2010.02.019

    View details for Web of Science ID 000279038400005

    View details for PubMedID 20231040

  • Lymph Node Staging by Positron Emission Tomography in Cervical Cancer: Relationship to Prognosis JOURNAL OF CLINICAL ONCOLOGY Kidd, E. A., Siegel, B. A., Dehdashti, F., Rader, J. S., Mutch, D. G., Powell, M. A., Grigsby, P. W. 2010; 28 (12): 2108-2113

    Abstract

    PURPOSE A previous retrospective study demonstrated that positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) was more sensitive than computed tomography for lymph node staging in patients with cervical cancer; the findings on FDG-PET were strongly associated with progression-free survival. Therefore, a prospective cohort study was initiated to evaluate FDG-PET lymph node staging in a larger patient population. PATIENTS AND METHODS The study was conducted between July 2000 and March 2009. All 560 patients with cervical cancer underwent pretreatment FDG-PET lymph node staging. Treatment included surgery alone, surgery and postoperative radiation therapy, and definitive radiation or combination radiation and chemotherapy. PET findings were correlated with the risk of disease progression and with survival. Results Overall, 47% of patients had lymph node involvement by FDG-PET at diagnosis. The frequency of lymph node metastasis increased with clinical stage and was similar to that in historical surgical series. Within a stage, patients with PET-positive lymph nodes had significantly worse disease-specific survival than those with PET-negative lymph nodes (P < .001). Disease-specific survival was stratified into distinct groups based on the most distant level of PET-detected nodal disease (none, pelvic, para-aortic, or supraclavicular; P < .001). The hazard ratios for disease recurrence increased incrementally based on the most distant level of nodal disease: pelvic 2.40 (95% CI, 1.63 to 3.52), para-aortic 5.88 (95% CI, 3.80 to 9.09), and supraclavicular 30.27 (95% CI 16.56 to 55.34). CONCLUSION Nodal involvement detected by FDG-PET in cervical cancer relates to clinical stage, is comparable to historical data, and stratifies patient recurrence and survival outcomes.

    View details for DOI 10.1200/JCO.2009.25.4151

    View details for Web of Science ID 000276764000023

    View details for PubMedID 20308664

  • Pelvic Lymph Node F-18 Fluorodeoxyglucose Uptake as a Prognostic Biomarker in Newly Diagnosed Patients With Locally Advanced Cervical Cancer CANCER Kidd, E. A., Siegel, B. A., Dehdashti, F., Grigsby, P. W. 2010; 116 (6): 1469-1475

    Abstract

    The objective of the current study was to evaluate the prognostic significance of the maximum standardized uptake value (SUV(max)) of F-18 fluorodeoxyglucose (FDG) as measured by positron emission tomography (PET) in pelvic lymph nodes in patients with cervical cancer.The authors studied cervical cancer patients with pelvic lymph node metastasis, as evidenced on FDG-PET, who were treated between November 2003 and October 2008. The maximum dimension and SUV(max) for the most FDG-avid pelvic lymph node (SUV(PLN)) and the SUV(max) of the primary cervical tumor (SUV(cervix)) were recorded from the FDG-PET/computed tomography (CT) scan. The SUV(PLN) was analyzed for its association with treatment response, pelvic disease recurrence, disease-specific survival, and overall survival.The population was comprised of 83 women with International Federation of Gynecology and Obstetrics (FIGO) stages IB1 to IIIB cervical cancer. The average SUV(PLN) was 6.9 (range, 2.1-33.0), whereas the average SUV(cervix) was 14.0 (range, 3.2-38.4). The SUV(cervix) and SUV(PLN) were found to be weakly correlated (correlation coefficient [R(2)] = 0.301). The average size of the pelvic lymph nodes was 2.1 cm (range, 0.6-7.9 cm), and was also found to be only weakly associated with the SUV(PLN) (R(2) = 0.225). The SUV(PLN) was found to be correlated with an increased risk of persistent disease after treatment (P = .0025), specifically within the pelvic lymph node region (P = .0003). The SUV(PLN) was found to be predictive of an increased risk of ever developing pelvic disease recurrence (P = .0035). Patients with a higher SUV(PLN) were found to have significantly worse disease-specific (P = .0230) and overall survival (P = .0378) using Kaplan-Meier evaluation. A Cox proportional hazards model for the risk of pelvic disease recurrence was performed including SUV(PLN,) patient age, and tumor stage, and found only an increased SUV(PLN) to be an independent predictor.SUV(PLN) is a prognostic biomarker, predicting treatment response, pelvic recurrence risk, and disease-specific survival in patients with cervical cancer.

    View details for DOI 10.1002/cncr.24972

    View details for Web of Science ID 000275238800014

    View details for PubMedID 20108309

  • Cervical Cancer Histology and Tumor Differentiation Affect F-18-Fluorodeoxyglucose Uptake Translational Meeting of the American-Society-Therapeutic-Radiology-and-Oncology Kidd, E. A., Spencer, C. R., Huettner, P. C., Siegel, B. A., Dehdashti, F., Rader, J. S., Grigsby, P. W. WILEY-BLACKWELL. 2009: 3548–54

    Abstract

    This study aimed to evaluate the variation in cervical cancer glucose metabolism for different tumor histologies and levels of differentiation, as measured by the uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET).The study population consisted of 240 patients with International Federation of Gynecology and Obstetrics stages Ib1 through IVb cervical cancer, who underwent a pretreatment FDG-PET. Tumor histology included 221 squamous cell (SC), 4 adenosquamous (AS), and 15 adenocarcinoma (AC) tumors. There were 14 well, 145 moderately, and 81 poorly differentiated tumors. The stage distribution was as follows: 70 stage I tumors (9 AC, 2 AS, and 59 SC), 102 stage II tumors (3 AC, 1 AS, and 98 SC), 64 stage III tumors (3 AC, 1 AS, and 60 SC), and 4 stage IV tumors (4 SC). From the FDG-PET, maximal standardized uptake value (SUVmax) was determined. The variation in SUVmax was analyzed for differences based on tumor histology and differentiation.For all patients, the mean SUVmax was 11.62 (range, 2.50-50.39). The mean SUVmax by histology was as follows: SC, 11.91 (range, 2.50-50.39); AS, 8.85 (range, 6.53-11.26); and AC, 8.05 (range, 2.83-13.92). Squamous versus nonsquamous tumors demonstrated a significant difference in SUVmax (P=.0153). SUVmax and tumor volume were not found to be correlated (R2=0.013). The mean SUVmax was 8.58 for well-differentiated, 11.56 for moderately differentiated, and 12.23 for poorly differentiated tumors. The mean SUVmax was significantly different for well-differentiated versus poorly differentiated cervical tumors (P=.0474).Cervical tumor FDG uptake varied by histology and differentiation. SC tumors demonstrated a significantly higher SUVmax compared with nonsquamous cell tumors, and poorly differentiated tumors also had a higher SUVmax.

    View details for DOI 10.1002/cncr.24400

    View details for Web of Science ID 000268060500023

    View details for PubMedID 19472399

  • Exploring feature-based approaches in PET images for predicting cancer treatment outcomes. Pattern recognition El Naqa, I., Grigsby, P., Apte, A., Kidd, E., Donnelly, E., Khullar, D., Chaudhari, S., Yang, D., Schmitt, M., Laforest, R., Thorstad, W., Deasy, J. O. 2009; 42 (6): 1162–71

    Abstract

    Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patient's response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

    View details for DOI 10.1016/j.patcog.2008.08.011

    View details for PubMedID 20161266

    View details for PubMedCentralID PMC2701316

  • Intratumoral metabolic heterogeneity of cervical cancer CLINICAL CANCER RESEARCH Kidd, E. A., Grigsby, P. W. 2008; 14 (16): 5236-5241

    Abstract

    Previous research has shown that the intertumoral maximum standardized uptake value (SUVMax) of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for cervical cancer predicts disease outcome. The purpose of this study was to evaluate the pretreatment intratumoral metabolic heterogeneity of FDG.This is a prospective cohort study of 72 patients with International Federation of Gynecology and Obstetrics stages Ib1 to IVa cervical cancer treated with chemoradiation. Three-dimensional FDG-PET threshold tumor volumes were calculated using image segmentation and an adaptive thresholding method for the primary cervix tumor from the pretreatment FDG-PET/computerized tomography. Intratumor heterogeneity was obtained for each patient's cervical tumor by taking the derivative (dV/dT) of the volume-threshold function from 40% to 80%. The association between intratumoral heterogeneity and tumor-specific factors and patient outcomes were determined.The mean cervix tumor SUV(Max) was 12.4 (range, 3.0-38.4). The mean differential tumor heterogeneity was -1.074 (range, -0.107 to -5.623). There was no association between dV/dT and SUVMax (R2 = 0.069), but there was a relationship with dV/dT and tumor volume (R2 = 0.881). There was no correlation of dV/dT with tumor histology (P = 0.4905). Heterogeneity was significantly associated with the risk of lymph node metastasis at diagnosis (P = 0.0009), tumor response to radiation as evaluated by FDG-PET obtained 3 months after completing treatment (P = 0.0207), risk of pelvic recurrence (P = 0.0017), and progression-free survival (P = 0.03).Cervical intratumoral FDG metabolic heterogeneity on the pretreatment FDG-PET predicts risk of lymph node involvement at diagnosis, response to therapy, and risk of pelvic recurrence.

    View details for DOI 10.1158/1078-0432.CCR-07-5252

    View details for Web of Science ID 000258523800029

    View details for PubMedID 18698042

  • The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival CANCER Kidd, E. A., Siegel, B. A., Dehdashti, F., Grigsby, P. W. 2007; 110 (8): 1738-1744

    Abstract

    The objective of this study was to evaluate cervical tumor uptake of F-18 fluorodeoxyglucose (FDG) measured as the maximal standardized uptake value (SUV(max)) by positron emission tomography (PET) and its association with treatment response and prognosis in patients with cervical cancer.The study population consisted of 287 patients with stage IA2 through IVB cervical cancer who underwent pretreatment FDG-PET studies. SUV(max), tumor volume, and sites of lymph node metastasis were recorded. Therapy included surgery, chemoradiation, or palliation.The mean SUV(max) was 11.4 (range, 1-50.4). The mean tumor volume by stage was 42.1 cm(3) for stage I tumors (using International Federation of Gynecology and Obstetrics [FIGO] staging criteria), 63.7 cm(3) for stage II tumors, 129.2 cm(3) for stage III tumors, and 166.2 cm(3) for stage IV tumors. There was no correlation between tumor volume and SUV(max) (correlation coefficient [R(2)] = 0.01). No significant difference in SUV(max) was observed between squamous histology (n = 247 patients) and nonsquamous histology (n = 40 patients; P = .089). Higher SUV(max) was associated with an increased risk of lymph node metastasis at diagnosis (P = .0009). A Cox proportional-hazards model for death from cervical cancer was used to evaluate tumor histology, lymph node metastasis, tumor volume, and SUV(max). The results indicated that SUV(max) was the only significant independent factor (P = .0027). Three prognostic groups were established using SUV(max). The overall survival rates at 5 years were 95% for an SUV(max) 5.2 and 13.3 (P < .0001). Increasing SUV(max) was associated with persistent abnormal FDG uptake in the cervix on 3-month FDG-PET studies in 238 patients who received curative chemoradiation (P = .04).The SUV(max) of the cervical tumor at diagnosis was a sensitive biomarker of treatment response and prognosis for patients with cervical cancer.

    View details for DOI 10.1002/cncr.22974

    View details for Web of Science ID 000250033300014

    View details for PubMedID 17786947

  • The efficacy of radiation therapy in the management of grade I astrocytomas JOURNAL OF NEURO-ONCOLOGY Kidd, E. A., Mansur, D. B., Leonard, J. R., Michalski, J. M., Simpson, J. R., Perry, A. 2006; 76 (1): 55-58

    Abstract

    The purpose of this study was to analyze the outcome of patients with grade I astrocytomas treated with radiation therapy, specifically looking at the prognostic significance of age, timing of radiation therapy (immediately after surgery or delayed until progression) and tumor location.The records of patients with grade I astrocytomas treated at Washington University Medical Center between 1982 and 2002 were reviewed. Twenty patients with grade I pilocytic astrocytoma (n=19) or subependymal giant cell astrocytoma (n=1) were treated with radiation therapy with curative intent.The median follow-up was 6.4 years. The 5-year overall survival for all patients was 100%. The 5-year progression-free survival (PFS) following radiation therapy for all patients was 68%. Patients who received radiation therapy immediately after biopsy or surgery had a 5-year PFS of 77% versus 50% for patients who received radiation therapy after initial disease progression (P=0.013). Patients with infratentorial tumors had an improved outcome with a 5-year PFS of 80% versus 59% for those with supratentorial tumors (P=0.0076). Patient age did not significantly influence outcome. All tumor recurrences were local.While this study reports an excellent overall survival, approximately one third of patients with grade I astrocytomas had progressive disease following radiation therapy. In particular, patients with supratentorial tumors and delayed radiation therapy had a worse PFS. Additional investigation is needed to improve the outcome in these patients.

    View details for DOI 10.1007/s11060-005-2913-1

    View details for Web of Science ID 000234553400008

    View details for PubMedID 16132503

  • Variance in the expression of 5-fluorouracil pathway genes in colorectal cancer CLINICAL CANCER RESEARCH Kidd, E. A., Yu, J. S., Li, X., Shannon, W. D., Watson, M. A., McLeod, H. L. 2005; 11 (7): 2612-2619

    Abstract

    Although colorectal cancer has the third highest cancer mortality rate, the treatment remains far from optimized with patients showing variable responses to standard treatment. Molecular differences in pharmacologically relevant genes may contribute to the variability in response. This study used Taqman PCR to investigate the expression of 24 5-fluorouracil (5-FU) pathway genes in colorectal cancer using paired nontumor and tumor sample from 52 patients with Dukes' C colon cancer. In comparing tumor versus nonmalignant tissue, 14 of the 24 genes showed significant variation in gene expression. For 11 of these same genes (FPGS, DHFR, GGH, NME1, NME2, RRM2, UMPH2, UNG, UMPS, TP53, and TK1), a significant proportion of the patients showed an over expression of the particular gene in tumor tissue with a tumor-to-nonmalignant (T/N) ratio >1.2, whereas one gene (DPYD) showed the converse with a large number of patients showing a lower expression in the tumor tissue (T/N < 0.8). Multiple gene correlations for the genes of the 5-FU pathway were found with the Spearman rank correlation of >0.6 (all P > 0.001), suggesting possible coregulation mechanisms. Hierarchical clustering analysis created at least three groups of genes, which were consistent with groupings by the other statistical methods. Additionally, the hierarchical clustering showed two distinct groups of patients based on their gene expression. These variations in gene expression could provide valuable insights for optimizing treatment selection for patients with colorectal cancer.

    View details for Web of Science ID 000228320100023

    View details for PubMedID 15814641

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