298 results on '"Mark F. Munsell"'
Search Results
2. Data from A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study
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Kathleen M. Schmeler, Elizabeth Y. Chiao, Erich M. Sturgis, Keith Sigel, Lauren Cobb, Aaron Shafer, Jolyn Taylor, Nicole D. Fleming, Anthony Price, Mallory Ogburn, Kristina R. Dahlstrom, Ashish Deshmukh, Mila Salcedo, Joel Fokom-Domgue, Mark F. Munsell, Ming Guo, Andrea Milbourne, Craig A. Messick, and Samantha Batman
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Background:High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women.Methods:This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA).Results:324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia.Conclusions:Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer.Impact:These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.
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- 2023
3. Supplementary Table from A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study
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Kathleen M. Schmeler, Elizabeth Y. Chiao, Erich M. Sturgis, Keith Sigel, Lauren Cobb, Aaron Shafer, Jolyn Taylor, Nicole D. Fleming, Anthony Price, Mallory Ogburn, Kristina R. Dahlstrom, Ashish Deshmukh, Mila Salcedo, Joel Fokom-Domgue, Mark F. Munsell, Ming Guo, Andrea Milbourne, Craig A. Messick, and Samantha Batman
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Supplementary Table from A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study
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- 2023
4. Data from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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Russell R. Broaddus, David M. Gershenson, Andrea Milbourne, Peggy Conrad, Molly S. Daniels, Mary Rubin, Stephanie Boyd-Rogers, Terri Cornelison, Henry Lynch, Lee-may Chen, Mark F. Munsell, Graciela M. Nogueras-Gonzalez, Melinda S. Yates, David S. Loose, and Karen H. Lu
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Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population. Cancer Prev Res; 6(8); 774–81. ©2013 AACR.
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- 2023
5. Supplementary Figure Legend from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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Russell R. Broaddus, David M. Gershenson, Andrea Milbourne, Peggy Conrad, Molly S. Daniels, Mary Rubin, Stephanie Boyd-Rogers, Terri Cornelison, Henry Lynch, Lee-may Chen, Mark F. Munsell, Graciela M. Nogueras-Gonzalez, Melinda S. Yates, David S. Loose, and Karen H. Lu
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PDF file - 42K
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- 2023
6. Supplementary Figure 1 from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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Russell R. Broaddus, David M. Gershenson, Andrea Milbourne, Peggy Conrad, Molly S. Daniels, Mary Rubin, Stephanie Boyd-Rogers, Terri Cornelison, Henry Lynch, Lee-may Chen, Mark F. Munsell, Graciela M. Nogueras-Gonzalez, Melinda S. Yates, David S. Loose, and Karen H. Lu
- Abstract
PDF file - 9245K, Supplementary Figure S1. Baseline endometrial abnormalities detected in the pre-treatment biopsies from these high-risk women.
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- 2023
7. Commentary on This Article from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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Russell R. Broaddus, David M. Gershenson, Andrea Milbourne, Peggy Conrad, Molly S. Daniels, Mary Rubin, Stephanie Boyd-Rogers, Terri Cornelison, Henry Lynch, Lee-may Chen, Mark F. Munsell, Graciela M. Nogueras-Gonzalez, Melinda S. Yates, David S. Loose, and Karen H. Lu
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Commentary on This Article from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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- 2023
8. Supplementary Table 1 from Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome
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Russell R. Broaddus, David M. Gershenson, Andrea Milbourne, Peggy Conrad, Molly S. Daniels, Mary Rubin, Stephanie Boyd-Rogers, Terri Cornelison, Henry Lynch, Lee-may Chen, Mark F. Munsell, Graciela M. Nogueras-Gonzalez, Melinda S. Yates, David S. Loose, and Karen H. Lu
- Abstract
XLSX file - 34K, Supplementary Table S1. Probes and primers for real-time PCR biomarker assays.
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- 2023
9. Data from Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma
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Cheryl Lyn Walker, Russell R. Broaddus, Mark F. Munsell, Thomas W. Burke, Brian M. Slomovitz, Bhuvanesh Dave, Weiguo Wu, and Karen H. Lu
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Purpose: The involvement of phosphatase and tensin homologue deleted on chromosome ten (PTEN) in endometrial carcinoma has implicated phosphatidylinositol 3-kinase signaling and mammalian target of rapamycin (mTOR) activation in this disease. Understanding the extent of mTOR involvement and the mechanism responsible for activation is important, as mTOR inhibitors are currently being evaluated in clinical trials for endometrial carcinoma. Although tuberous sclerosis complex 2 (TSC2) is the “gatekeeper” for mTOR activation, little is known about defects in the TSC2 tumor suppressor or signaling pathways that regulate TSC2, such as LKB1/AMP-activated protein kinase, in the development of endometrial carcinoma.Experimental Design: We determined the frequency of mTOR activation in endometrial carcinoma (primary tumors and cell lines) and investigated PTEN, LKB1, and TSC2 defects as underlying cause(s) of mTOR activation, and determined the ability of rapamycin to reverse these signaling defects in endometrial carcinoma cells.Results: Activation of mTOR was a consistent feature in endometrial carcinomas and cell lines. In addition to PTEN, loss of TSC2 and LKB1 expression occurred in a significant fraction of primary tumors (13% and 21%, respectively). In tumors that retained TSC2 expression, phosphorylation of tuberin at S939 was observed with a high frequency, indicating that mTOR repression by TSC2 had been relieved via AKT phosphorylation of this tumor suppressor. In PTEN-null and LKB1-null endometrial carcinoma cell lines with functional inactivation of TSC2, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 were able to inhibit AKT and mTOR signaling and reverse TSC2 phosphorylation. In contrast, although rapamycin inhibited mTOR signaling, it did not relieve phosphorylation of TSC2 at S939.Conclusions: Inactivation of TSC2 via loss of expression or phosphorylation occurred frequently in endometrial carcinoma to activate mTOR signaling. High-frequency mTOR activation supports mTOR as a rational therapeutic target for endometrial carcinoma. However, whereas rapamycin and its analogues may be efficacious at inhibiting mTOR activity, these drugs do not reverse the functional inactivation of TSC2 that occurs in these tumors.
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- 2023
10. Supplementary Data from Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma
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Cheryl Lyn Walker, Russell R. Broaddus, Mark F. Munsell, Thomas W. Burke, Brian M. Slomovitz, Bhuvanesh Dave, Weiguo Wu, and Karen H. Lu
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Supplementary Data from Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma
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- 2023
11. 2108. Evaluation of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection in Patients Living With Cancer at a Large Comprehensive Cancer Center
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Jaime A Peña, Nancy N Vuong, Pablo C Okhuysen, and Mark F Munsell
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Infectious Diseases ,Oncology - Abstract
Background Bezlotoxumab is a fully human monoclonal antibody that binds and neutralizes Clostridioides difficile toxin B. Administration of bezlotoxumab along with standard of care antibiotic (SoC) treatment of C. difficile infections (CDI) is associated with lower rates of CDI recurrence (rCDI). We aimed to determine the real-world incidence of rCDI in patients with cancer within 12 weeks after receiving bezlotoxumab. Methods This is a retrospective, single-center, descriptive study of patients with cancer that received bezlotoxumab from Jan 2018 through Oct 2021 at a large cancer center. rCDI was defined as a clinical illness associated with a positive stool nucleic acid amplification test with or without a confirmatory toxin assay for which CDI SoC was prescribed. Results A total of 131 patients were included in the study (median age of 63 years, 47% male, 77% Caucasian, 21% ICU admission), with 31% having one or more CDI episodes ≤ 6 months prior to receiving bezlotoxumab. The most common primary cancer type was leukemia (36%) followed by a solid organ tumor (35%), lymphoma (21%), and myeloma (8%). Cytotoxic chemotherapy or immune checkpoint inhibitors were prescribed within 6 months in 78% of cases and 60% of patients were given antibiotics not related to CDI. Fidaxomicin was most frequently administered as SoC (56%), followed by oral vancomycin (44%) with or without intravenous metronidazole. Within 12 weeks following bezlotoxumab treatment, rCDI occurred in 14 (10.7%, 95% Cl 5.4% to 16.0%) patients. Using univariate analysis, patients with rCDI were more likely to have received levofloxacin before and during bezlotoxumab treatment (86% versus 47%; OR 6.76, 95% CI 1.45 - 31.56, p=0.009). Conclusion In this real-world study, the rate of rCDI following use of bezlotoxumab during SoC antibiotics was comparable to that seen in clinical trials. Use of levofloxacin as prophylaxis for prolonged neutropenia in hematologic malignancies was associated with significantly higher rates of rCDI in patients that received bezlotoxumab. Our study suggests that neutropenia and antibiotic induced dysbiosis are risk factors for rCDI despite bezlotoxumab administration. Disclosures Pablo C. Okhuysen, MD, AstraZeneca: Stocks/Bonds|Beam Therapeutics: Stocks/Bonds|Biontech: Stocks/Bonds|Deinove: Grant/Research Support|Ferring: Advisor/Consultant|Glaxo Smith Kleine: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Melinta: Grant/Research Support|Merck Sharp & Dohme Corp: Grant/Research Support|Moderna: Stocks/Bonds|Napo Pharmaceuticals: Advisor/Consultant|Napo Pharmaceuticals: Grant/Research Support|Novavax: Stocks/Bonds|Pfizer: Stocks/Bonds|Summit: Advisor/Consultant|Summit: Grant/Research Support.
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- 2022
12. Using Social Media to Facilitate Communication About Women's Testing: Tool Validation Study
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Tara Coffin, Deborah Bowen, Karen Lu, Elizabeth M Swisher, Nadine Rayes, Barbara Norquist, Stephanie V Blank, Douglas A Levine, Jamie Nadine Bakkum-Gamez, Gini F Fleming, Olufunmilayo I Olopade, Iris Romero, Alan D'Andrea, Denise R Nebgen, Christine Peterson, Mark F Munsell, Kathleen Gavin, Jamie Crase, Deborah Polinsky, and Rebecca Lechner
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Medicine (miscellaneous) ,Health Informatics - Abstract
Background Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. Objective This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. Methods We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. Results Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just Conclusions Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. Trial Registration ClinicalTrials.gov NCT02993068; https://clinicaltrials.gov/ct2/show/NCT02993068
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- 2021
13. Radical Hysterectomy and Age: Outcomes Comparison Based on a Minimally Invasive vs an Open Approach
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Mark F. Munsell, Pedro T. Ramirez, Michael Frumovitz, Carlos Eduardo Mattos da Cunha Andrade, and Ricardo dos Reis
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Reproductive medicine ,Uterine Cervical Neoplasms ,Gynecologic oncology ,Hysterectomy ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Robotic Surgical Procedures ,Laparotomy ,medicine ,Humans ,Minimally Invasive Surgical Procedures ,Radical Hysterectomy ,Laparoscopy ,Fisher's exact test ,Retrospective Studies ,Cervical cancer ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Age Factors ,Obstetrics and Gynecology ,Cancer ,Middle Aged ,medicine.disease ,Surgery ,Cross-Sectional Studies ,Treatment Outcome ,030220 oncology & carcinogenesis ,symbols ,Female ,business - Abstract
To compare outcomes of radical hysterectomy (RH) across age groups based on surgical approach: minimally invasive surgery (MIS) vs laparotomy (LP).Cross-sectional retrospective review (Canadian Task Force classification II-2).Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center.Patients with early-stage cervical cancer who underwent RH at a tertiary cancer center between 1990 and 2013.Patients were stratified by age group (50, 50-59, and ≥60 years) and by surgical approach (minimally invasive surgery [MIS] vs laparotomy [LP]).Patients with early-stage cervical cancer who underwent RH were retrospectively reviewed to obtain demographic data, surgical data, and clinical outcomes. We used the Fisher exact, Wilcoxon rank-sum, and Cochran-Mantel-Haenszel tests to compare categorical and continuous variables stratified by surgical approach and age group. A total of 548 patients were evaluated, including 427 (77.9%) who underwent LP (age50, 84.3%; 50-59, 11.2%; ≥60, 4.5%) and 121 (22.1%) who underwent MIS (age50, 71.9%; 50-59, 17.3%; ≥60, 10.8%). In the MIS group, 71 patients (58.7%) underwent laparoscopy and 50 (41.3%) underwent robotic surgery. Patients in the MIS group were significantly older and heavier than those in the LP group. The operative time was significantly longer in the MIS group. There was no between-group difference in intraoperative complications in any of the 3 age groups. LP patients had more infectious complications (respiratory, systemic, and wound) than MIS patients in the50-year age group (53.3% vs 21.8%). The difference between the LP and MIS groups with respect to the postoperative noninfectious complication rate was greatest in the ≥60-year age group (p = .0324).The between-group difference in postoperative noninfectious complication rate in the oldest age group was twice that in either of the other 2 age groups (p = .0324), even though the MIS patients were older, heavier, and had a longer operative time compared with the LP patients.
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- 2018
14. Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations
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Charlotte C. Sun, Andrea Bradford, Mark F. Munsell, Denise R. Nebgen, Karen H. Lu, Beth Soletsky, Laura L. Holman, Gary B. Chisholm, and Jean A. Hurteau
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medicine.medical_specialty ,endocrine system diseases ,Ovariectomy ,medicine.medical_treatment ,Pilot Projects ,Bilateral Salpingectomy ,Salpingectomy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Adverse effect ,BRCA2 Protein ,Ovarian Neoplasms ,030219 obstetrics & reproductive medicine ,BRCA1 Protein ,Obstetrics ,business.industry ,BRCA mutation ,Obstetrics and Gynecology ,Oophorectomy ,Cancer ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Ovarian cancer ,Risk Reduction Behavior - Abstract
Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure.In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms.Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses.In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.
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- 2018
15. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer
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Elizabeth D. Euscher, Charles F Levenback, Pamela T. Soliman, Nicole D. Fleming, Karen H. Lu, Michael Frumovitz, Pedro T. Ramirez, Charlotte C. Sun, Shayan M. Dioun, Shannon N. Westin, and Mark F. Munsell
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Adult ,Indocyanine Green ,Oncology ,medicine.medical_specialty ,Validation study ,medicine.medical_treatment ,Sentinel lymph node ,Article ,03 medical and health sciences ,0302 clinical medicine ,Carcinosarcoma ,Positron Emission Tomography Computed Tomography ,Internal medicine ,medicine ,Carcinoma ,Humans ,Prospective Studies ,Coloring Agents ,Prospective cohort study ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gynecology ,030219 obstetrics & reproductive medicine ,Sentinel Lymph Node Biopsy ,business.industry ,Endometrial cancer ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Endometrial Neoplasms ,Sentinel lymph node mapping ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,Lymphadenectomy ,Sentinel Lymph Node ,Neoplasms, Cystic, Mucinous, and Serous ,business ,Carcinoma, Endometrioid ,Adenocarcinoma, Clear Cell - Abstract
Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC.Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed.123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23).This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.
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- 2017
16. Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in recurrent small cell neuroendocrine carcinoma of the cervix
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Lauren Averett Byers, Mark F. Munsell, Michael Frumovitz, Jennifer K. Burzawa, Robert L. Coleman, Preetha Ramalingam, and Jennifer R. Brown
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Paclitaxel ,endocrine system diseases ,genetic structures ,Bevacizumab ,Combination therapy ,Uterine Cervical Neoplasms ,Disease-Free Survival ,Article ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Cervix ,Platinum ,Retrospective Studies ,Brain Neoplasms ,business.industry ,Obstetrics and Gynecology ,Carcinoma, Neuroendocrine ,Surgery ,Survival Rate ,Regimen ,030104 developmental biology ,medicine.anatomical_structure ,Small cell neuroendocrine carcinoma ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Topotecan ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
To assess if the combination of topotecan, paclitaxel, and bevacizumab (TPB) was active in recurrent SCCC and to compare the survival of patients with SCCC who received TPB to a group of women with SCCC who did not receive this regimen.We retrospectively analyzed women with recurrent SCCC who received chemotherapy as primary therapy. Women treated with TPB for first recurrence were compared to women treated with non-TPB chemotherapy.Thirteen patients received TPB, and 21 received non-TPB chemotherapy, most commonly platinum with or without a taxane. Median progression-free survival (PFS) was 7.8months for TPB and 4.0months for non-TPB regimens (hazard ratio [HR] 0.21, 95% CI 0.09-0.54, P=0.001). Median overall survival (OS) was 9.7months for TPB and 9.4months for non-TPB regimens (HR 0.53, 95% CI 0.23-1.22, P=0.13). Eight women (62%) who received TPB versus four (19%) who received non-TPB regimens were on treatment for6months (P=0.02), and four patients (31%) in the TPB group versus two (10%) in the non-TPB group were on treatment for12months (P=0.17). In the TPB group, three patients (23%) had complete response, two (15%) had complete response outside the brain with progression in the brain, 3 (23%) had a partial response, 2 (15%) had stable disease, and 3 (23%) had progressive disease.These findings indicate that TPB for recurrent SCCC significantly improved PFS over non-TPB regimens, and trends towards improved OS. Furthermore, a significant number of patients had a durable clinical benefit.
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- 2017
17. Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study
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Shannon N. Westin, Russell Broaddus, Lois M. Ramondetta, David A. Iglesias, Pamela T. Soliman, Melinda S. Yates, Mark F. Munsell, Karen H. Lu, Qian Zhang, and Rosemarie Schmandt
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Leptin ,0301 basic medicine ,medicine.medical_treatment ,Apoptosis ,AMP-Activated Protein Kinases ,Endometrium ,Gastroenterology ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Lectins ,Insulin ,Prospective Studies ,Insulin-Like Growth Factor I ,Stage (cooking) ,Mitogen-Activated Protein Kinase 3 ,medicine.diagnostic_test ,Caspase 3 ,Obstetrics and Gynecology ,Middle Aged ,Immunohistochemistry ,Metformin ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Carcinoma, Endometrioid ,medicine.drug ,Adult ,medicine.medical_specialty ,GPI-Linked Proteins ,Article ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Hypoglycemic Agents ,Aged ,Cell Proliferation ,Gynecology ,business.industry ,Endometrial cancer ,Phosphoproteins ,medicine.disease ,Endometrial Neoplasms ,Clinical trial ,Ki-67 Antigen ,030104 developmental biology ,business ,Proto-Oncogene Proteins c-akt ,Endometrial biopsy - Abstract
Objective Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. Methods In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry. Results Twenty patients completed the trial. Median age and BMI were 57years (range: 27–67) and 34.5kg/m 2 (range: 21.9–50.0). Median duration of metformin was 9.5days (range: 7–24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 ( p =0.046), omentin ( p =0.007), insulin ( p =0.012), C-peptide ( p =0.018), and leptin ( p =0.0035). Compared to baseline, post-treatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p =0.0002), decreased phospho-S6rp in 14/20 patients (70%, p =0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p =0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation. Conclusion In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.
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- 2016
18. Comparison of Computed Tomography– and Magnetic Resonance Imaging–based Clinical Target Volume Contours at Brachytherapy for Cervical Cancer
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Lehendrick Turner, Mark F. Munsell, Gaiane M. Rauch, Cameron W. Swanick, Sastry Vedam, Patricia J. Eifel, Katherine O. Castle, Ann H. Klopp, and Anuja Jhingran
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Cervical cancer ,Cancer Research ,medicine.medical_specialty ,Radiation ,medicine.diagnostic_test ,Parametrial ,business.industry ,medicine.medical_treatment ,Brachytherapy ,Dose fractionation ,Magnetic resonance imaging ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Sørensen–Dice coefficient ,030220 oncology & carcinogenesis ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Tomography ,business ,Nuclear medicine ,Prospective cohort study - Abstract
Purpose We prospectively compared computed tomography (CT)– and magnetic resonance imaging (MRI)–based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. Methods and Materials Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identified the clinical and tumor factors associated with ( 1 ) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and ( 2 ) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. Results Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm 3 ) was larger than the mean MRI HR-CTV volume (35.1 cm 3 ; P t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours ( P P =.013). Conclusions We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.
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- 2016
19. 102 Cervical cancer screening using primary human papillomavirus (HPV) testing in mozambique: preliminary results of the capulana study
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Crisiane Rezende Vilela de Oliveira, SM Manhica, BX dos Santos, Ellen Baker, Cesaltina Lorenzoni, Kathleen M. Schmeler, RF Macaringue, Dercia Changule, Jht Fregnani, Melissa Lopez Varon, Ricardina Rangeiro, A Mariano, M Pontremoli Salcedo, Joe Thomas, Mark F. Munsell, M Chalyamba, Viviane Andrade, and N Phoolcharoen
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Cervical cancer ,medicine.medical_specialty ,medicine.diagnostic_test ,Referral ,business.industry ,Obstetrics ,medicine.medical_treatment ,Cancer ,Cryotherapy ,Disease ,medicine.disease ,Cervical cancer screening ,Hpv testing ,medicine ,business ,Pelvic examination - Abstract
Objectives Cervical cancer is the leading cause of cancer and related deaths among women in Mozambique. There is limited access to screening and few trained personnel to manage women with abnormal results. Our objective was to implement primary HPV screening in Mozambique and navigate women with abnormal results to appropriate diagnostic and treatment services. Methods We prospectively enrolled women aged 30 to 49 at Mavalane General Hospital in Maputo, Mozambique. All participants underwent a pelvic examination by a nurse and a cervical sample was collected and tested for HPV DNA using careHPV (Qiagen, Gaithersburg, MD, USA). Women who tested positive for HPV (HPV+) underwent visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) to assess eligibility for cryotherapy. All HPV+ women were treated with cryotherapy, loop electrosurgical excision procedure (LEEP), or referred for cancer management based on results. Results From April 2018 to February 2019, 427 women underwent HPV testing. The median age was 39 years. 86/426 patients (20.2%) were HIV positive. 93 patients (21.8%) were HPV+ and 97.8% (91/93) returned for VAT and treatment including cryotherapy (n=68, 74.7%), LEEP (n=10, 11.0%) and referral for cancer management (n=4, 4.4%). Treatment is pending in 9 patients for cryotherapy. Conclusions Cervical cancer screening with primary HPV DNA testing, including follow-up and treatment, was found to be feasible in Maputo, Mozambique. This study is ongoing to and includes training medical providers to diagnose and treat cervical preinvasive disease and cancer.
- Published
- 2019
20. A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway
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Javier Lasala, Maria D. Iniesta, Pedro T. Ramirez, Qiuling Shi, Camila Corzo, Xin Shelly Wang, Mark F. Munsell, Katherine E. Cain, Gabriel E. Mena, Brandelyn Pitcher, and Larissa A. Meyer
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Adult ,medicine.medical_specialty ,Exploratory laparotomy ,medicine.medical_treatment ,law.invention ,Young Adult ,03 medical and health sciences ,Gynecologic Surgical Procedures ,0302 clinical medicine ,Randomized controlled trial ,law ,Laparotomy ,medicine ,Humans ,Single-Blind Method ,Prospective Studies ,030212 general & internal medicine ,Anesthetics, Local ,Syringe ,Aged ,Pain Measurement ,Aged, 80 and over ,Bupivacaine ,Pain, Postoperative ,Wound Healing ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,Liposomal Bupivacaine ,Surgery ,Treatment Outcome ,Opioid ,Liposomes ,Morphine ,Female ,business ,medicine.drug - Abstract
Background Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). Objective This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. Study Design A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute–designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. Results In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. Conclusion Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient’s self-reported pain and functional recovery compared with standard bupivacaine.
- Published
- 2021
21. How low should we go: A systematic review and meta-analysis of the impact of restrictive red blood cell transfusion strategies in oncology
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David R. Lairson, Mark F. Munsell, Maria A. Lopez-Olivo, Jolyn S. Taylor, Helena M. VonVille, Lauren S. Prescott, and Diane C. Bodurka
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Oncology ,medicine.medical_specialty ,Red Blood Cell Transfusion ,MEDLINE ,Context (language use) ,030204 cardiovascular system & hematology ,Medical Oncology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Radiology, Nuclear Medicine and imaging ,Adverse effect ,Randomized Controlled Trials as Topic ,business.industry ,General Medicine ,Perioperative ,Confidence interval ,030220 oncology & carcinogenesis ,Meta-analysis ,Relative risk ,Erythrocyte Transfusion ,business - Abstract
Background Most non-oncologic clinical practice guidelines recommend restrictive allogeneic blood transfusion practices; however, there is a lack of consensus regarding the best transfusion practice in oncology. We conducted a systematic review of the literature to compare the efficacy and safety of restrictive versus liberal transfusion strategies in patients with cancer. Methods A literature search using MEDLINE, PUBMED and EMBASE identified all controlled studies comparing the use of restrictive with liberal transfusion in adult oncology participants up to August 10, 2015. Two review authors independently assessed studies for inclusion, extracted data and appraised the quality of the included studies. The primary outcomes of interest were blood utilization and all-cause mortality. Results Out of 4241 citations, six studies (3 randomized and 3 non-randomized) involving a total of 983 patients were included in the final review. The clinical context of the studies varied with 3 chemotherapy and 3 surgical studies. The overall risk of bias in all studies was moderate to high. Restrictive transfusion strategies were associated with a 36% reduced risk of receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.49–0.83). There was no difference in mortality between the strategies (RR 1.00, 95% CI 0.32–3.18). There were no differences in adverse events reported between the restrictive and liberal transfusion strategies. Conclusion Restrictive strategy appears to decrease blood utilization without increasing morbidity or mortality in oncology. This review is limited by a paucity of high quality studies on this topic. Better designed studies are warranted.
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- 2016
22. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents
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Karen H. Lu, Mark F. Munsell, Beibei Guo, Amir A. Jazaeri, and Ying Yuan
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Statistics and Probability ,Protocol (science) ,Iterative design ,Epidemiology ,Computer science ,business.industry ,Bayesian probability ,Machine learning ,computer.software_genre ,01 natural sciences ,Bayesian design ,Task (project management) ,Clinical trial ,010104 statistics & probability ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Adaptive selection ,Overhead (computing) ,Artificial intelligence ,0101 mathematics ,business ,computer ,Simulation - Abstract
Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd.
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- 2016
23. Front-line Treatment with Gemcitabine, Paclitaxel, and Doxorubicin for Patients With Unresectable or Metastatic Urothelial Cancer and Poor Renal Function: Final Results from a Phase II Study
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Mark F. Munsell, Robert L. Carolla, Arlene O. Siefker-Radtke, Matthew T. Campbell, Lance C. Pagliaro, and Deborah Harris
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Adult ,Male ,Oncology ,Urologic Neoplasms ,medicine.medical_specialty ,Filgrastim ,Paclitaxel ,Urology ,medicine.medical_treatment ,Phases of clinical research ,Antineoplastic Agents ,Kidney ,Deoxycytidine ,Article ,Polyethylene Glycols ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,Mucositis ,Carcinoma ,Humans ,Medicine ,Renal Insufficiency ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,Carcinoma, Transitional Cell ,Chemotherapy ,business.industry ,Middle Aged ,medicine.disease ,Gemcitabine ,Recombinant Proteins ,Carboplatin ,Regimen ,chemistry ,Doxorubicin ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Female ,business ,Pegfilgrastim ,medicine.drug - Abstract
To estimate the response rate of gemcitabine, paclitaxel, and doxorubicin in patients with advanced urothelial carcinoma, we conducted a phase II clinical trial. Patients with renal insufficiency cannot receive standard cisplatin-based chemotherapy for urothelial carcinoma, and carboplatin-based regimens have proved unsatisfactory. Secondary end points for this study included overall survival, safety of the regimen, and safety of same-day pegfilgrastim dosing.A two-stage design was chosen with target response rate of 40%. Key inclusion criteria were metastatic or unresectable urothelial carcinoma, no prior chemotherapy, glomerular filtration rate60 mL/min, and no dialysis. Gemcitabine (900 mg/m(2)), paclitaxel (135 mg/m(2)), and doxorubicin (40 mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or optionally day 2.Forty patients were enrolled and 39 were treated. Median age was 72 years (range 51-89). There were 7 complete and 15 partial responses, for a response rate of 56.4% (95% confidence interval, 39.6-72.2). Most cycles (82.8%) were given with same-day pegfilgrastim. Notable grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (10.3% each). There were 4 episodes of neutropenic fever (4 of 198 cycles [2%]; 4 of 39 patients [10.3%]) and no treatment-related deaths. Median overall survival was 14.4 months.The combination of gemcitabine, paclitaxel, and doxorubicin is effective first-line chemotherapy for patients with advanced urothelial carcinoma and renal insufficiency. Neutropenic prophylaxis was acceptable whether pegfilgrastim was given immediately or 24 hours after chemotherapy.
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- 2016
24. Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): A review of 47 cases
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David M. Gershenson, Elizabeth D. Euscher, Donato Callegaro-Filho, Kathleen M. Schmeler, Pedro T. Ramirez, Patricia J. Eifel, Mark F. Munsell, Sergio Mancini Nicolau, Alpa M. Nick, and Renato Moretti Marques
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Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Small-cell carcinoma ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Adjuvant therapy ,Humans ,Carcinoma, Small Cell ,Stage (cooking) ,Child ,Retrospective Studies ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Obstetrics and Gynecology ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,Radiation therapy ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Hypercalcemia ,Female ,business ,Rare disease - Abstract
Objective Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. Methods We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. Results Median age at diagnosis was 30years (range 5–46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2months (range, 0.1 to 210.7) with a median overall survival of 14.9months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. Conclusion Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations.
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- 2016
25. Results from MAGENTA: A national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk
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Kathleen Gavin, Elizabeth M. Swisher, Jamie Crase, Stephanie V. Blank, Sherman Law, Douglas A. Levine, Deborah Polinsky, Deborah J. Bowen, Barbara M. Norquist, Mark F. Munsell, Nadine Rayes, Jamie N. Bakkum-Gamez, Harsha M Pradeep, Olufunmilayo I. Olopade, Denise R. Nebgen, Alan D. D'Andrea, Karen H. Lu, Tara Coffin, Alicia Y. Zhou, and Christine B. Peterson
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Genetic counseling ,medicine.disease ,Test (assessment) ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Genetic risk ,Ovarian cancer ,business ,Pre and post ,030215 immunology - Abstract
1506 Background: Hereditary breast and ovarian cancer (HBOC) is preventable when genetic risk is identified. We aimed to test whether pre and/or post-test genetic counseling is needed to optimally deliver online accessible genetic testing. Methods: MAGENTA (Making GENetic Testing Accessible) is a four-arm non-inferiority trial evaluating electronic genetic education and results delivery alone or combined with pre-test only, or post-test only telephone genetic counseling compared to mandatory pre- and post-test counseling (control arm) in women at risk of HBOC (NCT02993068). Regardless of assigned arm, all subjects with a pathogenic mutation received post-test telephone counseling. All subjects were enrolled electronically as part of either a family history cohort (FHC) or a cascade cohort (CC, known familial mutation). The primary outcome was cancer risk distress at 3 months and the trial was powered for the FHC. Secondary outcomes included completion of testing (i.e., received results), anxiety, depression, quality of life, and decisional regret, all measured by standardized scales. Results: Enrollment is complete and a total of 3,822 participants were randomized, 3,111 in FHC and 711 in CC. Participants were enrolled from all 50 states, but most were white/non-Hispanic (88%). Among participants that completed genetic testing, 173 (7.2%) had a mutation in a breast or ovarian cancer gene, with 114 (5.7%) of FHC and 59 (14.2%) of CC. In the primary intention-to-treat analysis of FHC, each of the three experimental arms was non-inferior to the control arm for distress at 3 months (p < 0.025/3 = 0.0083). In the CC, no and pre-test only counseling were also non-inferior (p < 0.025/3 = 0.0083). Distress was lowest in the arm with neither pre nor post-test counseling. Overall, 318 (18%) participants had very high distress at three month follow-up, and this rate was not significantly different across arms. Anxiety, depression and decisional regret did not have statistically significant differences across arms at follow-up. Test completion was highest in the no counseling arm (86.4%) and lowest in the control arm (60.6%). Conclusions: Electronic genetic education and results release without genetic counseling was non-inferior with regard to patient distress and was associated with higher test completion and lower distress. These results support use of a genetic testing paradigm providing individualized genetic counseling only for patients with positive test results. Clinical trial information: NCT02993068.
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- 2020
26. Nuclear β-catenin localization and mutation of the CTNNB1 gene: a context-dependent association
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Wei Lien Wang, Charanjeet Singh, Russell Broaddus, Bojana Djordjevic, Grace Kim, Wei Zhang, Alexander J. Lazar, Katherine C. Kurnit, and Mark F. Munsell
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Mutant ,Context (language use) ,Gene mutation ,medicine.disease_cause ,Sensitivity and Specificity ,Medical and Health Sciences ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Uterine Cancer ,Clinical Research ,Genetics ,Biomarkers, Tumor ,Medicine ,Humans ,beta Catenin ,Cancer ,Retrospective Studies ,Cell Nucleus ,Mutation ,Tumor ,business.industry ,Endometrial cancer ,medicine.disease ,3. Good health ,Endometrial Neoplasms ,Protein Transport ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,business ,Nuclear localization sequence ,Biomarkers - Abstract
Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes β-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the β-catenin protein from the membrane to the nucleus and activation of Wnt/β-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of β-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of β-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5-10% of tumor cells with β-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of β-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of β-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of β-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of β-catenin is absent.
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- 2018
27. Effect of an Enhanced Recovery After Surgery Program on Opioid Use and Patient-Reported Outcomes
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Qiuling Shi, Xin Shelley Wang, Javier Lasala, Pedro T. Ramirez, Mark F. Munsell, Katherine E. Cain, Maria D. Iniesta, Alpa M. Nick, Karen H. Lu, and Larissa A. Meyer
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Adult ,medicine.medical_specialty ,Quality management ,Adolescent ,Opioid consumption ,Genital Neoplasms, Female ,Treatment outcome ,Perioperative Care ,Article ,03 medical and health sciences ,0302 clinical medicine ,Gynecologic Surgical Procedures ,Postoperative Complications ,medicine ,Humans ,030212 general & internal medicine ,Patient Reported Outcome Measures ,Postoperative Period ,Enhanced recovery after surgery ,Fatigue ,Aged ,Pain Measurement ,Aged, 80 and over ,Pain, Postoperative ,Extramural ,business.industry ,Opioid use ,Obstetrics and Gynecology ,Perioperative ,Length of Stay ,Middle Aged ,Physical Functional Performance ,Quality Improvement ,Analgesics, Opioid ,Treatment Outcome ,030220 oncology & carcinogenesis ,Perioperative care ,Emergency medicine ,Female ,business - Abstract
OBJECTIVE: To investigate the effect of an enhanced recovery after surgery (ERAS) program on perioperative outcomes with an emphasis on opioid consumption and patient-reported outcomes in the immediate and extended postoperative period. METHODS: We initiated our ERAS program as part of a quality improvement initiative in November 2014. We compared clinical outcomes among a cohort of 607 women undergoing open gynecologic surgery before or after implementation of ERAS. For 293 patients, patient reported outcomes were compared using the MD Anderson Symptom Inventory-Ovarian Cancer (MDASI-OC). RESULTS: Median age was 58 years (18–85). Median length of stay decreased by 25% for patients in the ERAS pathway, (p
- Published
- 2018
28. The influence of surgeon volume on outcomes after pelvic exenteration for a gynecologic cancer
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Alpa M. Nick, Pamela T. Soliman, Mark F. Munsell, Michael Frumovitz, Pedro T. Ramirez, Randa J. Jalloul, and Shannon N. Westin
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Adult ,medicine.medical_specialty ,Genital Neoplasms, Female ,medicine.medical_treatment ,Blood Loss, Surgical ,Workload ,Logistic regression ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,medicine ,Humans ,Blood Transfusion ,030212 general & internal medicine ,Cervix ,Aged ,Aged, 80 and over ,Pelvic exenteration ,business.industry ,Hazard ratio ,Urinary diversion ,Obstetrics and Gynecology ,Cancer ,Postoperative complication ,General Medicine ,Length of Stay ,Middle Aged ,Pregnancy Outcomes ,Surgeon Volume ,medicine.disease ,Texas ,Confidence interval ,Pelvic Exenteration ,3. Good health ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Original Article ,Clinical Competence ,Gynecologic Neoplasms ,business ,Follow-Up Studies - Abstract
Objective To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. Methods This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. Results A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p
- Published
- 2018
29. Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete
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Mireia Gonzalez-Comadran, Rene Pareja, Daniel Sanabria, Lina Echeverri, David Isla, Pedro T. Ramirez, Mark F. Munsell, Gabriel J. Rendón, and Michael Frumovitz
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Uterine Cervical Neoplasms ,Hysterectomy ,03 medical and health sciences ,0302 clinical medicine ,Gynecologic Surgical Procedures ,Risk Factors ,medicine ,Humans ,Stage (cooking) ,Neoplasm Staging ,Retrospective Studies ,Cervical cancer ,030219 obstetrics & reproductive medicine ,business.industry ,Parametrial ,Obstetrics and Gynecology ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,Oncology ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Adenocarcinoma ,Median body ,Female ,business - Abstract
Objective The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. Methods A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions Results A total of 30 patients were included in the study. The median age was 40.4years (range; 26–60) and median body mass index (BMI) was 26.4kg/m 2 (range; 17.7–40.0). A total 22 patients had tumors Conclusion Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.
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- 2017
30. Impact of Lymph Node Ratio and Adjuvant Therapy in Node-Positive Endometrioid Endometrial Cancer
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Mark F. Munsell, Nicole D. Fleming, Ann H. Klopp, Pamela T. Soliman, Shannon N. Westin, Michael Frumovitz, Pedro T. Ramirez, Kathleen M. Schmeler, Alpa M. Nick, and Ricardo dos Reis
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Adult ,Oncology ,Prognostic variable ,medicine.medical_specialty ,medicine.medical_treatment ,Article ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Adjuvant therapy ,Humans ,Stage IIIC ,Lymph node ,Survival rate ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Endometrial cancer ,Hazard ratio ,Obstetrics and Gynecology ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Endometrial Neoplasms ,Survival Rate ,Radiation therapy ,medicine.anatomical_structure ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,Lymph Node Excision ,Female ,Radiotherapy, Adjuvant ,Lymph Nodes ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Objectives To determine if the ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is a prognostic variable in patients with node-positive endometrial cancer and the impact of adjuvant therapy on survival. Methods After institutional review board approval, a retrospective review of patients diagnosed as having stage IIIC endometrioid or mixed endometrioid endometrial cancer at a single institution from January 2000 through October 2011 was performed. Clinicopathologic and adjuvant treatment data were collected. Univariate and multivariate analysis were used to identify prognostic factors for progression-free (PFS) and overall survival. Results One hundred twenty-four patients with stage IIIC1 (n = 64) and IIIC2 (n = 60) endometrial cancer were included in the analysis. Median age was 60 years (range, 25–84 years), and median follow-up was 49.4 months (range, 0.1–301.6 months). Age >70 years was identified as a prognostic factor for worse PFS (P = 0.0002) and overall survival (P = 0.0002) on multivariate analysis. Patients in this cohort receiving any adjuvant radiotherapy showed improved PFS (hazard ratio [HR], 0.34; 95% CI, 0.13–0.90; P = 0.03) compared with those receiving any adjuvant chemotherapy (HR, 2.33; 95% CI, 1.16–4.65; P = 0.02). In a subgroup analysis, patients with at least 10 nodes removed (n = 81) with an LNR greater than 50% had a PFS of 25.2 months compared with 135.6 months with an LNR of 50% or less (HR, 3.87; 95% CI, 1.15–13.04; P = 0.03). Conclusions Lymph node ratio may define a subgroup of stage IIIC endometrial cancers at increased risk for recurrence. Adjuvant radiotherapy was associated with decreased recurrence risk.
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- 2015
31. Radical trachelectomy in early-stage cervical cancer: A comparison of laparotomy and minimally invasive surgery
- Author
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Gabriel J. Rendón, Rene Pareja, Pedro F. Escobar, Marcelo Vieira, Michael Frumovitz, Mark F. Munsell, Pedro T. Ramirez, Lina Echeverri, Kathleen M. Schmeler, and Ricardo dos Reis
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,media_common.quotation_subject ,Uterine Cervical Neoplasms ,Trachelectomy ,Fertility ,Gynecologic Surgical Procedures ,Pregnancy ,Laparotomy ,medicine ,Humans ,Minimally Invasive Surgical Procedures ,Fertility preservation ,Stage (cooking) ,Retrospective Studies ,media_common ,Cervical cancer ,business.industry ,General surgery ,Fertility Preservation ,Obstetrics and Gynecology ,Retrospective cohort study ,Perioperative ,medicine.disease ,Surgery ,Oncology ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Radical trachelectomy is considered standard of care in patients with early-stage cervical cancer interested in future fertility. The goal of this study was to compare operative, oncologic, and fertility outcomes in patients with early-stage cervical cancer undergoing open vs. minimally invasive radical trachelectomy.A retrospective review was performed of patients from four institutions who underwent radical trachelectomy for early-stage cervical cancer from June 2002 to July 2013. Perioperative, oncologic, and fertility outcomes were compared between patients undergoing open vs. minimally invasive surgery.A total of 100 patients were included in the analysis. Fifty-eight patients underwent open radical trachelectomy and 42 patients underwent minimally invasive surgery (MIS=laparoscopic or robotic). There were no differences in patient age, body mass index, race, histology, lymph vascular space invasion, or stage between the two groups. The median surgical time for MIS was 272min [range, 130-441min] compared with 270min [range, 150-373min] for open surgery (p=0.78). Blood loss was significantly lower for MIS vs. laparotomy (50mL [range, 10-225mL] vs. 300mL [50-1100mL]) (p0.0001). Nine patients required blood transfusion, all in the open surgery group (p=0.010). Length of hospitalization was shorter for MIS than for laparotomy (1day [1-3 days] vs. 4days [1-9 days]) (p0.0001). Three intraoperative complications occurred (3%): 1 bladder injury, and 1 fallopian tube injury requiring unilateral salpingectomy in the MIS group and 1 vascular injury in the open surgery group. The median lymph node count was 17 (range, 5-47) for MIS vs. 22 (range, 7-48) for open surgery (p=0.03). There were no differences in the rate of postoperative complications (30% MIS vs. 31% open surgery). Among 83 patients who preserved their fertility (33 MIS vs. 50 open surgery), 34 (41%) patients attempted to get pregnant. Sixteen (47%) patients were able to do so (MIS: 2 vs. laparotomy: 14, p=0.01). The pregnancy rate was higher in the open surgery group when compared to the MIS group (51% vs. 28%, p=0.018). However, median follow-up was shorter is the MIS group compared with the open surgery group (25months [range, 10-69] vs. 66months [range, 11-147]). To date, there has been one recurrence in the laparotomy group and none in the MIS group.Our results suggest that radical trachelectomy via MIS results in less blood loss and a shorter hospital stay. Fertility rates appear higher in patients undergoing open radical trachelectomy.
- Published
- 2015
32. A Comparison Between Appendiceal and Nonappendiceal Neuroendocrine Tumors in Children and Young Adults
- Author
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Mark F. Munsell, Winston W. Huh, Catherine H. Boston, Cynthia E. Herzog, and Alexandria T. Phan
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Neuroendocrine tumors ,Gastroenterology ,Metastasis ,Young Adult ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,Single institution ,Young adult ,Child ,Survival rate ,Neoplasm Staging ,Retrospective Studies ,Chemotherapy ,business.industry ,Hematology ,Prognosis ,medicine.disease ,Survival Rate ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Appendiceal Neoplasms ,Pediatrics, Perinatology and Child Health ,Curative surgery ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local ,Pancreas ,business ,Follow-Up Studies - Abstract
BACKGROUND Pediatric neuroendocrine tumors (NETs) are rare tumors. The purpose of this study is to report the clinical characteristics and outcomes of pediatric patients treated for NET at a single institution. PROCEDURE A retrospective record review. RESULTS There were 33 evaluable patients with median age of 17.9 years (range, 9.9 to 21.9 y) and predominantly females (58%). There were 17 patients with well-differentiated appendiceal NET, whereas 16 were nonappendiceal. Most common nonappendiceal sites were unknown primary (N=6) and pancreas (N=4). Majority of tumors were low grade (N=24, 73%) and small (T1, N=22, 67%). Nonappendiceal tumors were more likely to be larger or high-grade tumors (5/16, 31%), or with metastasis. All appendiceal NET patients underwent curative surgery. All patients who experienced treatment failure had nonappendiceal NET, despite prior chemotherapy in 8 of 9 patients. The 5-year overall survival rates for patients with appendiceal and nonappendiceal NET were 100% and 66% (95% CI, 45%-95%; P=0.006); and 5-year relapse-free survival rate for patients with appendiceal and nonappendiceal NET were 100% and 41% (95% CI, 22%-75%; P=0.002). CONCLUSIONS Well-differentiated appendiceal tumors were the most common pediatric NET and have an excellent prognosis. Better therapies are needed for patients with nonappendiceal NET.
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- 2015
33. Make New Friends But Keep the Old: Minimally Invasive Surgery Training in Gynecologic Oncology Fellowship Programs
- Author
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Kari L. Ring, William M. Burke, Pedro T. Ramirez, R. Wendel Naumann, Lesley B. Conrad, Michael Frumovitz, and Mark F. Munsell
- Subjects
medicine.medical_specialty ,Genital Neoplasms, Female ,MEDLINE ,Gynecologic oncology ,Medical Oncology ,Article ,Objective assessment ,Gynecologic Surgical Procedures ,Uterine cancer ,medicine ,Humans ,Minimally Invasive Surgical Procedures ,Robotic surgery ,Fellowships and Scholarships ,Fellowship training ,Cervical cancer ,business.industry ,General surgery ,Obstetrics and Gynecology ,medicine.disease ,Oncology ,Education, Medical, Graduate ,Invasive surgery ,Female ,Clinical Competence ,business - Abstract
ObjectivesTo evaluate the role of minimally invasive surgery (MIS) in gynecologic oncology fellowship training and fellows’ predictions of their use of MIS in their future practice.MethodsAll fellows-in-training in American Board of Obstetrics and Gynecology–approved training programs were surveyed in 2012 through an online or mailed-paper survey. Data were analyzed and compared to results of a similar 2007 survey.ResultsOf 172 fellows, 69 (40%) responded. Ninety-nine percent of respondents (n = 68) indicated that MIS was either very important or important in gynecologic oncology, a proportion essentially unchanged from 2007 (100%). Compared to 2007, greater proportions of fellows considered laparoscopic radical hysterectomy and node dissection for cervical cancer (87% vs 54%; P < 0.0001) and trachelectomy and staging for cervical cancer (83% vs 32%; P < 0.0001) appropriate for MIS. Of the respondents, 92% believed that maximum or some emphasis should be placed on robotic-assisted surgery and 89% on traditional laparoscopy during fellowship training. Ten percent rated their fellowship training in laparoendoscopic single-site surgery as very poor; 44% said that the question was not applicable. Most respondents (60%) in 2012 performed at least 11 procedures per month, whereas most respondents (45%) in 2007 performed 6 to 10 procedures per month (P = 0.005). All respondents at institutions where robotic surgery was used were allowed to operate at the robotic console, and 63% of respondents reported that in robotic-assisted surgery cases when a fellow sat at the robot, the fellow performed more than 50% of the case at the console.ConclusionsThese findings indicate that MIS in gynecologic oncology is here to stay. Fellowship programs should develop a systematic approach to training in MIS and in individual MIS platforms as they become more prevalent. Fellowship programs should also develop and apply an objective assessment of minimum proficiency in MIS to ensure that programs are adequately preparing trainees.
- Published
- 2015
34. Prognostic factors influencing survival from regionally advanced squamous cell carcinoma of the penis after preoperative chemotherapy
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Curtis A. Pettaway, Lance C. Pagliaro, Rian J. Dickstein, and Mark F. Munsell
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Male ,Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Penile Neoplasm ,030232 urology & nephrology ,Antineoplastic Agents ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Penile cancer ,Penile Neoplasms ,Lymph node ,Retrospective Studies ,Cisplatin ,Chemotherapy ,Ifosfamide ,business.industry ,Prognosis ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Lymphadenectomy ,business ,Penis ,medicine.drug - Abstract
Objective To describe both clinical and pathological response rates, survival, and predictors of survival when using contemporary perioperative chemotherapy and surgical resection for patients with regionally advanced squamous cell carcinoma (SCC) of the penis. Patients and Methods Retrospective review of all patients diagnosed with SCC of the penis and regional lymph node metastases that were treated with chemotherapy with the intent to undergo lymphadenectomy. Clinical and pathological responses were reported. Recurrence-free and overall survival was estimated using Kaplan–Meier analysis. Cox proportional hazards regression was used to assess factors for survival. Results In all, 61 patients were identified, of which 54 (90%) received chemotherapy with paclitaxel/ifosfamide/cisplatin. In all, 39 patients (65%) had either a partial (PR) or complete response (CR) to chemotherapy. The 5-year survival varied significantly (P = 0.045–0.001) among patients achieving a CR/PR (50%), stable disease (25%), and progression (7.7%). In all, 10 patients (16.4%) were rendered pN0 with combined therapy and 20 patients (33%) were alive and disease free at a median follow-up of 67 months, while 32 (52%) died from disease. Long-term survival was associated with response to chemotherapy and favourable pathological findings after resection. Conclusion Contemporary chemotherapy resulted in clinically significant responses among patients with regionally advanced penile cancer. About 50% of such patients with an objective response to chemotherapy who undergo consolidative lymphadenectomy will remain alive at 5 years.
- Published
- 2015
35. Expression of a Surface Antigen (MA6) by Peripheral Blood CD34+Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation
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Michael W. Thomas, Mark F. Munsell, Patrick A. Zweidler-McKay, Jeannie A. Javni, Elizabeth J. Shpall, Simon N. Robinson, Paul J. Simmons, and Nathalie Brouard
- Subjects
Blood Platelets ,Platelet Engraftment ,CD34 ,Antigens, CD34 ,Platelet Transfusion ,Cell Biology ,Hematology ,Biology ,Fetal Blood ,Hematopoietic Stem Cells ,Hematopoiesis ,Andrology ,Transplantation ,Haematopoiesis ,Platelet transfusion ,Original Research Reports ,Cord blood ,Immunology ,Humans ,Progenitor cell ,Ex vivo ,Developmental Biology - Abstract
CD34(+) cell dose provides a measure of hematopoietic tissue that predicts the rate of engraftment upon transplant. It is positively correlated with multiple measures of hematopoietic recovery, including platelet engraftment. Here we identify a subpopulation of CD34(+) cells that coexpress a surface antigen--MA6, which is more positively correlated with platelet engraftment in a clinical setting than CD34(+) alone. The specific identity and function of MA6 remain to be determined, however, it is expressed by primitive megakaryocyte (MK) progenitors, but is lost with differentiation and is not expressed by platelets. Commitment of CD34(+)MA6(+) cells to the MK lineage was confirmed by in vitro assays and their significance in hematopoietic transplantation explored by flow cytometric analysis of cryopreserved samples of granulocyte colony stimulating factor-mobilized peripheral blood progenitor cell (PBPC) products along with a retrospective analysis of platelet engraftment data. Platelet engraftment by day 21 was predicted by receipt of ≥ 6 × 10(6) CD34(+) cells/kg or ≥ 0.3 × 10(6) CD34(+)MA6(+) cells/kg. Subsequent analysis of cord blood (CB) CD34(+) cells revealed
- Published
- 2015
36. Significance of lymph node ratio in defining risk category in node-positive early stage cervical cancer
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Shannon N. Westin, Michael Frumovitz, Pamela T. Soliman, Mark F. Munsell, Nicole D. Fleming, Pedro T. Ramirez, Patricia J. Eifel, Alpa M. Nick, Ricardo dos Reis, and Kathleen M. Schmeler
- Subjects
Adult ,Risk ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Uterine Cervical Neoplasms ,Hysterectomy ,Article ,Disease-Free Survival ,Young Adult ,Internal medicine ,Humans ,Medicine ,Young adult ,Stage (cooking) ,Survival rate ,Lymph node ,Aged ,Neoplasm Staging ,Retrospective Studies ,Cervical cancer ,Analysis of Variance ,business.industry ,Obstetrics and Gynecology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Rate ,medicine.anatomical_structure ,Lymphatic Metastasis ,Multivariate Analysis ,Lymph Node Excision ,Female ,Lymph Nodes ,Lymph ,business - Abstract
The ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is an important prognostic factor in several solid tumors. The objective of this study was to determine if LNR can be used to define a high-risk category of patients with node-positive early stage cervical cancer.We performed a retrospective review of patients diagnosed with node-positive stage I or II cervical cancer who underwent radical hysterectomy and pelvic +/- para-aortic lymphadenectomy at MD Anderson from January 1990 to December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free (PFS) and overall survival (OS).Ninety-five patients met the inclusion criteria and were included in the analysis. Median total nodes removed were 19 (range 1-58), and median number of positive nodes was 1 (range 1-12). Fifty-eight patients (61%) received radiation with concurrent cisplatin and 27 patients (28%) received radiotherapy alone. Twenty-one (22%) patients recurred. On multivariate analysis, a LNR6.6% was associated with a worse PFS (HR = 2.97, 95% CI 1.26-7.02, p = 0.01), and a LNR7.6% with a worse OS (HR = 3.96, 95% CI 1.31-11.98, p = 0.01). On multivariate analysis, positive margins were associated with worse PFS (p = 0.001) and OS (p = 0.002), and adjuvant radiotherapy (p = 0.01) with improved OS.LNR appears to be a useful tool to identify patients with worse prognosis in node-positive early stage cervical cancer. LNR may be used in addition to pathologic risk factors to tailor adjuvant treatment in this population.
- Published
- 2015
37. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials
- Author
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Reza J. Mehran, Cornelis J.A. Haasbeek, Alexander V. Louie, Omar Dawood, Egbert F. Smit, Larry S. Carpenter, Ben J. Slotman, Ritsuko Komaki, Harry J.M. Groen, John J. Kresl, Suresh Senan, Peter A Balter, Joe Y. Chang, Lei Feng, Donald A. Berry, Jack A. Roth, Katrien De Jaeger, Erik van Werkhoven, Ben E. E. M. van den Borne, Coen W. Hurkmans, Marinus A. Paul, Stephen E. McRae, Anne-Marie C. Dingemans, Joachim Widder, Mark F. Munsell, Guided Treatment in Optimal Selected Cancer Patients (GUTS), MUMC+: MA Med Staf Spec Longziekten (9), Pulmonologie, Humane Biologie, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiation Oncology, Cardio-thoracic surgery, Pulmonary medicine, and CCA - Innovative therapy
- Subjects
medicine.medical_specialty ,RESECTION ,BODY RADIATION-THERAPY ,medicine.medical_treatment ,Chest pain ,SABR volatility model ,NSCLC ,Radiosurgery ,law.invention ,Randomized controlled trial ,law ,TOMOGRAPHY ,medicine ,ASSISTED THORACOSCOPIC SURGERY ,Lung cancer ,ELDERLY-PATIENTS ,OUTCOMES ,business.industry ,MORTALITY ,Hazard ratio ,medicine.disease ,Surgery ,Clinical trial ,Radiation therapy ,Oncology ,medicine.symptom ,business - Abstract
Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a ( Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0–47·3) for the SABR group and 35·4 months (18·9–40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017–1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0·69 [95% CI 0·21–2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). Interpretation SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Funding Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
- Published
- 2015
38. Improved Compliance With Venous Thromboembolism Pharmacologic Prophylaxis for Patients With Gynecologic Malignancies Hospitalized for Nonsurgical Indications Did Not Reduce Venous Thromboembolism Incidence
- Author
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Lauren S. Prescott, Lisa M. Kidin, Mark F. Munsell, David J. Cleveland, Ginger L. Wilson, Pedro T. Ramirez, Kathleen M. Schmeler, Charles F Levenback, Michael H. Kroll, Rebecca L. Downs, Alma Yvette DeJesus, and Katherine E. Cain
- Subjects
Adult ,medicine.medical_specialty ,Genital Neoplasms, Female ,Population ,MEDLINE ,Article ,Cohort Studies ,Young Adult ,Patient safety ,Risk Factors ,medicine ,Humans ,Young adult ,Intensive care medicine ,education ,Contraindication ,Aged ,Neoplasm Staging ,Aged, 80 and over ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Anticoagulants ,Obstetrics and Gynecology ,Venous Thromboembolism ,Middle Aged ,Prognosis ,Quality Improvement ,Texas ,Hospitalization ,Oncology ,Practice Guidelines as Topic ,Cohort ,Patient Compliance ,Female ,Guideline Adherence ,business ,Follow-Up Studies ,Cohort study - Abstract
ObjectiveNational guidelines recommend prophylactic anticoagulation for all hospitalized patients with cancer to prevent hospital-acquired venous thromboembolism (VTE). However, adherence to these evidence-based recommended practice patterns remains low. We performed a quality improvement (QI) project to increase VTE pharmacologic prophylaxis rates among patients with gynecologic malignancies hospitalized for nonsurgical indications and evaluated the resulting effect on rates of development of VTE.Materials and MethodsIn June 2011, departmental VTE practice guidelines were implemented for patients with gynecologic malignancies who were hospitalized for nonsurgical indications. A standardized VTE prophylaxis module was added to the admission electronic order sets. Outcome measures included number of admissions receiving VTE pharmacologic prophylaxis within 24 hours of admission; and number of potentially preventable hospital-acquired VTEs diagnosed within 30 and 90 days of discharge. Outcomes were compared between a preguideline implementation cohort (n = 99), a postguideline implementation cohort (n = 127), and a sustainability cohort assessed 2 years after implementation (n = 109). Patients were excluded if upon admission they had a VTE, were considered low risk for VTE, or had a documented contraindication to pharmacologic prophylaxis.ResultsAdministration of pharmacologic prophylaxis within 24 hours of admission increased from 20.8% to 88.2% immediately following the implementation of guidelines, but declined to 71.8% in our sustainability cohort (P < 0.001). There was no difference in VTE incidence among the 3 cohorts [n = 2 (4.2%) vs n = 3 (3.9%) vs n = 3 (4.2%), respectively; P = 1.00].ConclusionsOur QI project improved pharmacologic VTE prophylaxis rates. A small decrease in prophylaxis during the subsequent 2 years suggests a need for continued surveillance to optimize QI initiatives. Despite increased adherence to guidelines, VTE rates did not decline in this high-risk population.
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- 2015
39. Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System
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Soumen Khatua, Mary Frances McAleer, M. Fatih Okcu, Nancy Kumbalasseriyil, Murali Chintagumpala, David R. Grosshans, Mark F. Munsell, Susan L. McGovern, and Anita Mahajan
- Subjects
Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Radiation ,Bevacizumab ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,medicine.disease ,Craniospinal Irradiation ,Radiation therapy ,Oncology ,Atypical teratoid rhabdoid tumor ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Nuclear medicine ,business ,Proton therapy ,Craniospinal ,medicine.drug - Abstract
Purpose Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.
- Published
- 2014
40. Position-related injury is uncommon in robotic gynecologic surgery
- Author
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Shannon N. Westin, Pamela T. Soliman, Pedro T. Ramirez, Kathleen M. Schmeler, Alpa M. Nick, Michael A. Ulm, Nicole D. Fleming, Mark F. Munsell, and Vijayashri Rallapali
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Ecchymosis ,Article ,Patient Positioning ,Young Adult ,Gynecologic Surgical Procedures ,Risk Factors ,medicine ,Humans ,Robotic surgery ,Child ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Obstetrics and Gynecology ,Retrospective cohort study ,Robotics ,Middle Aged ,medicine.disease ,Surgery ,Oncology ,Brachial plexus injury ,Anesthesia ,Musculoskeletal injury ,Female ,medicine.symptom ,business ,Body mass index ,Abdominal surgery - Abstract
Objective To assess the rate and risk factors for position-related injury in robotic gynecologic surgery. Methods A prospective database from 12/2006 to 1/2014 of all planned robotic gynecologic procedures was retrospectively reviewed for patients who experienced neurologic injury, musculoskeletal injury, or vascular compromise related to patient positioning in the operating room. Analysis was performed to determine risk-factors and incidence for position-related injury. Results Of the 831 patients who underwent robotic surgery during the study time period, only 7 (0.8%) experienced positioning-related injury. The injuries included minor head contusions ( n =3), two lower extremity neuropathies ( n =2), brachial plexus injury ( n =1) and one large subcutaneous ecchymosis on the left flank and thigh ( n =1). There were no long term sequelae from the positioning-related injuries. The only statistically significant risk factor for positioning-related injury was prior abdominal surgery ( P =0.05). There were no significant associations between position-related injuries and operative time ( P =0.232), body mass index ( P =0.847), age ( P =0.152), smoking history ( P =0.161), or medical comorbidities ( P =0.229–0.999). Conclusions The incidence of position-related injury among women undergoing robotic surgery was extremely low (0.8%). Due to the low incidence we were unable to identify modifiable risk factors for position-related injury following robotic surgery. A standardized, team-oriented approach may significantly decrease position-related injuries following robotic gynecologic surgery.
- Published
- 2014
41. A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment
- Author
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Charlotte C. Sun, Karen H. Lu, Erica M. Bednar, Mark F. Munsell, Holly D. Oakley, Shannon N. Westin, and Catherine Burke
- Subjects
0301 basic medicine ,Adult ,medicine.medical_specialty ,Genetic counseling ,Genes, BRCA2 ,Genes, BRCA1 ,Genetic Counseling ,Gynecologic oncology ,Carcinoma, Ovarian Epithelial ,Poly(ADP-ribose) Polymerase Inhibitors ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Mass Screening ,Genetic Testing ,Neoplasms, Glandular and Epithelial ,Genetic testing ,Aged ,Retrospective Studies ,Gynecology ,Aged, 80 and over ,Ovarian Neoplasms ,medicine.diagnostic_test ,business.industry ,Medical record ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Quality Improvement ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,PARP inhibitor ,Hereditary Breast and Ovarian Cancer Syndrome ,Neoplasm Grading ,business ,Ovarian cancer ,Neoplasms, Cystic, Mucinous, and Serous ,Carcinoma, Endometrioid ,Progressive disease ,Adenocarcinoma, Clear Cell - Abstract
Objective Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. Methods Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed. Data were abstracted from the tumor registry, medical records, and research databases. Descriptive statistics were used to evaluate patient characteristics and GC, GT, and PARP inhibitor use. Various clinic interventions were developed, influenced by the Plan-Do-Study-Act cycle method, which included physician-coordinated GT, integrated GC, and assisted GC referrals. Results A cohort of 1636 patients presented to the gynecologic oncology clinics for evaluation of HGOC during our study period, and 1423 (87.0%) were recommended to have GC and GT. Of these, 1214 (85.3%) completed GT and 217 (17.9%) were found to have a BRCA1 or BRCA2 mutation. Among BRCA-positive patients, 167 had recurrent or progressive disease, and 56 of those received PARP inhibitor therapy. Conclusions The rates of GC and GT recommendation and completion among patients with HGOC at our institution exceeded 80% following the implementation of a universal genetic testing initiative. Universal genetic testing of patients with HGOC is one strategy to identify those who may benefit from PARP inhibitor therapy.
- Published
- 2017
42. Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer
- Author
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Anil K. Sood, Nicole D. Fleming, Robert L. Coleman, Mark F. Munsell, Shannon N. Westin, Yunjie Sun, Wei Hu, Priya Bhosale, and Celestine S. Tung
- Subjects
Oncology ,Adult ,medicine.medical_specialty ,Bevacizumab ,Non-Randomized Controlled Trials as Topic ,Paclitaxel ,medicine.medical_treatment ,Phases of clinical research ,Angiogenesis Inhibitors ,Disease-Free Survival ,Drug Administration Schedule ,Article ,Carboplatin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Adjuvant therapy ,Biomarkers, Tumor ,Humans ,030212 general & internal medicine ,Aged ,Ovarian Neoplasms ,Chemotherapy ,Predictive marker ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Tolerability ,chemistry ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Ovarian cancer ,business ,medicine.drug - Abstract
Objectives To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. Methods After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays. Results Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58–4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05–13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05). Conclusions Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.
- Published
- 2017
43. Factors prognostic of survival in advanced-stage uterine serous carcinoma
- Author
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Laura L. Holman, Mark F. Munsell, David A. Iglesias, Russell Broaddus, Ann H. Klopp, Nicole D. Fleming, Navdeep Pal, Karen H. Lu, Shannon N. Westin, Pamela T. Soliman, and Nyla Balakrishnan
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Oncology ,Adult ,medicine.medical_specialty ,Multivariate analysis ,Combination therapy ,medicine.medical_treatment ,Disease ,Article ,Uterine serous carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Stage (cooking) ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Survival Analysis ,Cystadenocarcinoma, Serous ,Radiation therapy ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Uterine Neoplasms ,Female ,business - Abstract
Objectives The study objective was to analyze the impact of prognostic factors, including treatment modality, on outcome in patients with advanced-stage uterine serous carcinoma (USC). Methods A retrospective review of patients diagnosed with stage III or IV USC between 1993 and 2012 was performed. Summary statistics were used to describe demographic and clinical characteristics. Overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier analysis. Cox proportional hazards regression was used to model the association of potential prognostic factors with OS and RFS. Results The study included 260 patients with median follow-up of 26.6months (range 1–172.8). Median age was 63years (range 30–88) and 52.3% had stage III disease. In all, 60% were treated with surgery followed by chemotherapy, 18.1% received surgery, chemotherapy, and radiotherapy, 11.5% had surgery and radiotherapy, and 10.4% had neoadjuvant chemotherapy. The overall complete response rate was 68.9%, and the cumulative incidence of recurrence was 82.7%. Treatment that included surgery, chemotherapy, and radiation and stage III disease were associated with improved RFS on multivariate analysis. For OS, therapy with surgery, chemotherapy, and radiation, mixed histology, and stage III disease were associated with better OS on multivariate analysis. Conclusions Patients with advanced-stage USC have a poor prognosis, regardless of clinical factors or treatment received. However, combination therapy that includes chemotherapy and radiation appears to be associated with improved survival in these women.
- Published
- 2017
44. Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome
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Patrick M. Lynch, Elizabeth Keeler, Russell Broaddus, Sue Rimes, Mark F. Munsell, Karen H. Lu, and Denise R. Nebgen
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Adult ,medicine.medical_specialty ,Biopsy ,Sedation ,Colonic Polyps ,Colonoscopy ,Endometrium ,Article ,Cancer screening ,Humans ,Medicine ,Early Detection of Cancer ,Aged ,Retrospective Studies ,Hyperplasia ,medicine.diagnostic_test ,business.industry ,General surgery ,Obstetrics and Gynecology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Lynch syndrome ,Endometrial Neoplasms ,medicine.anatomical_structure ,Oncology ,Female ,medicine.symptom ,business ,Endometrial biopsy - Abstract
Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years.We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation.Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected.Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer.
- Published
- 2014
45. Prospective Exploratory Analysis of Cardiac Biomarkers and Electrocardiogram Abnormalities in Patients Receiving Thoracic Radiation Therapy with High-Dose Heart Exposure
- Author
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Syed Wamique Yusuf, Joe Y. Chang, Steven H. Lin, Mark F. Munsell, Mary Frances McAleer, Hubert Y. Pan, Daniel R. Gomez, Ritsuko Komaki, James D. Cox, James W. Welsh, Zhongxing Liao, and David R. Grosshans
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Thorax ,medicine.medical_specialty ,Heart Diseases ,medicine.drug_class ,medicine.medical_treatment ,Article ,Electrocardiography ,Internal medicine ,Natriuretic Peptide, Brain ,Troponin I ,Biomarkers, Tumor ,medicine ,Natriuretic peptide ,Humans ,Prospective Studies ,cardiovascular diseases ,Radiation Injuries ,Prospective cohort study ,Aged ,medicine.diagnostic_test ,biology ,business.industry ,Heart ,Middle Aged ,Thoracic Neoplasms ,Cardiac toxicity ,Brain natriuretic peptide ,Troponin ,Surgery ,Radiation therapy ,Oncology ,cardiovascular system ,Cardiology ,biology.protein ,Female ,Radiotherapy, Conformal ,Lung cancer ,business - Abstract
Introduction Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received more than or equal to 45 Gy to the thorax, with pretreatment estimates of more than or equal to 20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median TnI or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated ( p = 0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.
- Published
- 2014
46. Conversion from robotic surgery to laparotomy: A case–control study evaluating risk factors for conversion
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Pamela T. Soliman, Alpa M. Nick, Shannon N. Westin, Pedro T. Ramirez, Nicole D. Fleming, Larissa A. Meyer, Vijayashri Rallapalli, Mark F. Munsell, Nate Jones, and Kathleen M. Schmeler
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Risk Assessment ,Article ,Gynecologic surgical procedures ,Intraoperative Period ,Young Adult ,Gynecologic Surgical Procedures ,Risk Factors ,Laparotomy ,Humans ,Medicine ,Robotic surgery ,Young adult ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,General surgery ,technology, industry, and agriculture ,Case-control study ,Obstetrics and Gynecology ,Retrospective cohort study ,Robotics ,Middle Aged ,Surgery ,body regions ,Oncology ,Case-Control Studies ,Female ,business ,Risk assessment ,human activities - Abstract
To determine risk factors associated with conversion to laparotomy for women undergoing robotic gynecologic surgery.The medical records of 459 consecutive robotic surgery cases performed between December 2006 and October 2011 by 8 different surgeons at a single institution were retrospectively reviewed. Cases converted to laparotomy were compared to those completed robotically. Descriptive statistics were used to summarize the demographic and clinical characteristics.Forty of 459 (8.7%, 95% CI 6.3%-11.7%) patients had conversion to open surgery. Reason for conversion included poor visualization due to adhesions (13), inability to tolerate Trendelenburg (7), enlarged uterus (7), extensive peritoneal disease (5), bowel injury (2), ureteral injury (1), vascular injury (1), bladder injury (1), technical difficulty with the robot (2), and inability to access abdominal cavity (1). 5% of cases were converted prior to docking the robot. On univariate analysis, preoperative diagnosis (p=0.012), non-White race (p=0.004), history of asthma (p=0.027), ASA score (p=0.032), bowel injury (p=0.012), greater BMI (p0.001), need for blood transfusion (p0.001), and expected blood loss (p0.001) were associated with conversion. On multivariate analysis, non-White race (OR 2.88, 95% CI 1.39-5.96, p=0.004), bowel injury (OR 35.40, 95% CI 3.00-417.28, p=0.005), and increasing BMI (OR 1.06, 95% CI 1.03-1.09, p0.001) were significantly associated with increased risk for conversion. Prior surgery was not associated with conversion to open surgery (p=0.347).Conversion to laparotomy was required for 8.7% of patients undergoing robotic surgery for a gynecologic indication. Increasing BMI and non-white race were identified as the two preoperative risk factors associated with conversion.
- Published
- 2014
47. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice
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X. Ronald Zhu, G. Brandon Gunn, Narayan Sahoo, Randal S. Weber, Radhe Mohan, James D. Cox, Mark F. Munsell, Michael Gillin, Xiaodong Zhang, David I. Rosenthal, Adam S. Garden, Merrill S. Kies, Wei Liu, Steven J. Frank, M.B. Palmer, and Jan S. Lewin
- Subjects
Adult ,Male ,Cancer Research ,Quality Assurance, Health Care ,Adenoid cystic carcinoma ,medicine.medical_treatment ,Nasopharyngeal neoplasm ,Pilot Projects ,Radiotherapy Setup Errors ,Xerostomia ,Article ,Proton Therapy ,medicine ,Mucositis ,Humans ,Radiology, Nuclear Medicine and imaging ,Proton therapy ,Aged ,Stomatitis ,Radiation ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Head and neck cancer ,Uncertainty ,Nasopharyngeal Neoplasms ,Radiotherapy Dosage ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Carcinoma, Adenoid Cystic ,Tongue Neoplasms ,Radiation therapy ,Clinical trial ,Oropharyngeal Neoplasms ,Oncology ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Female ,Radiotherapy, Intensity-Modulated ,Nuclear medicine ,business ,Follow-Up Studies - Abstract
Background We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.
- Published
- 2014
48. Timing of Infectious Complications Following Breast-Conserving Therapy with Catheter-Based Accelerated Partial Breast Irradiation
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Elizabeth S. Bloom, Simona F. Shaitelman, Welela Tereffe, Isabelle Bedrosian, Alex B. Haynes, Linda Graviss, Gildy Babiera, Roy F. Chemaly, Kelly K. Hunt, Mark F. Munsell, Henry Mark Kuerer, Rosa F. Hwang, and Abigail S. Caudle
- Subjects
medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Brachytherapy ,Breast Neoplasms ,Mastectomy, Segmental ,Catheterization ,Postoperative Complications ,Surgical oncology ,Infectious complication ,Humans ,Surgical Wound Infection ,Combined Modality Therapy ,Medicine ,skin and connective tissue diseases ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Follow up studies ,Partial Breast Irradiation ,Middle Aged ,Prognosis ,Surgery ,Catheter ,Oncology ,Female ,business ,Catheter placement ,Follow-Up Studies - Abstract
Accelerated partial breast irradiation (APBI) has been used as an alternative to whole-breast irradiation as part of breast-conserving therapy. Indications and outcomes are topics of ongoing investigation. Previous publications have focused on early postoperative infections and reported low rates of delayed infection. We investigated the pattern of infection after catheter-based APBI at our institution.Patients who underwent single-entry catheter-based APBI were identified from an institutional prospective registry including data regarding comorbidities and outcomes. Time of infection was calculated from the date of definitive catheter insertion and classified as early (≤30 days) or delayed.A total of 91 breast cancer patients were treated with APBI and enrolled in the registry from 2009 to 2011. The median follow-up was 484 days. Breast infection occurred in 13 (14.3 %), with 3 (3.3 %) occurring within 30 days of catheter placement and 10 (11.0 %) in a delayed fashion. Four patients required hospital admission, five underwent percutaneous aspiration, and one underwent incision and drainage. Eight were treated as outpatients with oral antibiotics alone.Consistent with other reports, we found an overall infection rate of 14.3 % with single-entry catheter-based APBI. There were substantially fewer infections in the early postoperative period than reported elsewhere, but there were more delayed infections. The intensive follow-up in our study likely identified late infections that may not have otherwise been recognized. Vigilance for infectious complications must continue beyond the immediate treatment period in patients undergoing catheter-based APBI. These infections can range in severity but typically can be managed in an outpatient setting.
- Published
- 2014
49. Vaginal Intraepithelial Neoplasia (VaIN 2/3)
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Helen Rhodes, Latira Chenevert, and Mark F. Munsell
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Adult ,medicine.medical_specialty ,Vaginal Neoplasms ,Adolescent ,medicine.drug_class ,MEDLINE ,Cohort Studies ,Young Adult ,Chart review ,medicine ,Humans ,Single institution ,Young adult ,Aged ,Retrospective Studies ,Aged, 80 and over ,Vaginal intraepithelial neoplasia ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,Estrogens ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Administration, Intravaginal ,Treatment Outcome ,Estrogen ,Female ,business ,Carcinoma in Situ ,Cohort study - Abstract
To determine the outcomes of women treated for vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) with intravaginal estrogen.A retrospective chart review was performed of 106 patients with VaIN 2/3 evaluated at a single institution between 2000 and 2008. Medical records were reviewed for demographic information, risk factors, HPV status, treatment type, pathologic diagnosis, and outcome information. Patients with VaIN 1 and invasive disease at the time of initial presentation were excluded. In addition, patients who were lost to follow-up or who developed other genital tract malignancies during the study period were excluded from the final analysis.After exclusions, 83 patient records were included in the statistical analysis. The mean age at diagnosis was 54.3 years. Of these patients, 88.0% were postmenopausal and 88.0% had undergone previous hysterectomy. Moreover, 63.9% of the patients reported previous treatment for preinvasive disease (cervical, vaginal, or vulvar dysplasia). Of all the patients, 44.6% reported prior and/or current tobacco use and 48.2% tested positive for high-risk HPV types. Treatment modalities included intravaginal estrogen, CO(2) laser ablation, topical 5-fluorouracil, wide local excision, loop electrosurgical excision procedure, and vaginectomy. Some patients underwent more than 1 treatment modality. Of those patients treated with intravaginal estrogen alone (n = 40), 90.0% had regression or cure of high grade disease. Of those patients treated with intravaginal estrogen and 1 or more other treatment modalities (n = 32), 81.3% experienced regression or cure. In contrast, 71.4% of patients undergoing treatment without intravaginal estrogen experienced regression or cure of high-grade disease. Conditions of 2 patients progressed to invasive vaginal carcinoma during the study period. The mean length of follow-up for all patients was 47.6 months.This cohort of women with VaIN 2/3 further delineates the demographic and clinical risk factors associated with VaIN 2/3. High rates of regression and cure were found in patients treated with intravaginal estrogen, whether alone or in combination with other treatment modalities. Treatment of VaIN 2/3 with intravaginal estrogen therapy offers an alternative to standard therapies with a success rate that is comparable to that previously reported with other more potentially morbid therapies.
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- 2014
50. Utility of 18F-FDG PET/CT in follow-up of patients with low-grade serous carcinoma of the ovary
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Homer A. Macapinlac, Kathleen M. Schmeler, Satoshi Takeuchi, Robert L. Coleman, David M. Gershenson, Mark F. Munsell, Martin Lucchini, and Pedro T. Ramirez
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Adult ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Serous carcinoma ,Ovary ,Multimodal Imaging ,Sensitivity and Specificity ,Article ,Young Adult ,Fluorodeoxyglucose F18 ,medicine ,Carcinoma ,Humans ,In patient ,Aged ,Retrospective Studies ,Ovarian Neoplasms ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,Retrospective cohort study ,Middle Aged ,Low grade serous carcinoma ,medicine.disease ,female genital diseases and pregnancy complications ,carbohydrates (lipids) ,medicine.anatomical_structure ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Fdg pet ct ,Radiology ,Neoplasm Recurrence, Local ,Radiopharmaceuticals ,Tomography, X-Ray Computed ,business - Abstract
Ovarian low-grade serous carcinoma (LGSC) is a rare and indolent tumor. The utility of 18F-FDG PET/CT in monitoring patients with LGSC has not been established. We assessed the accuracy and clinical impact of 18F-FDG PET/CT in patients with ovarian LGSC after initial treatment.A retrospective analysis was performed on patients with ovarian LGSC who had undergone 18F-FDG PET/CT scans during follow-up after primary treatment. The impact of 18F-FDG PET/CT on the management plan was assessed. The sensitivity, specificity, and accuracy of 18F-FDG PET/CT findings in the detection of recurrence were calculated. Total lesion glycolysis (TLG) was determined to assess metabolic activity of tumors. Potential prognostic factors for disease-free and overall survival after recurrence were assessed.Forty-eight patients were included in the analysis, 39 with recurrent disease and 9 without recurrence. A total of 91 18F-FDG PET/CT scans were performed, and 30% of these (27/91) had an impact on the management plan. Sensitivity, specificity, and accuracy in the detection of LGSC recurrence were 94%, 100%, and 97%, respectively, for 18F-FDG PET/CT; 89%, 95%, and 93%,respectively, for CT; and 68%, 89%, and 73%, respectively, for serum CA-125. There was no significant difference in sensitivity between PET/CT and CT. Survival after recurrence was poorer in patients with a TLG value greater than 67.7g.18F-FDG PET/CT may provide useful information during the follow-up of patients with LGSC after initial treatment. TLG may be a predictor of survival after recurrence.
- Published
- 2014
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