No professional society or group recommends routine ovarian cancer screening, yet physicians&... more No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms. To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening. Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125). United States. 3200 physicians randomly sampled equally from the 2008 American Medical Association Physician Masterfile lists of family physicians, general internists, and obstetrician-gynecologists; 61.7% responded. After exclusions, 1088 respondents were included; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally. Reported nonadherence to screening recommendations (defined as sometimes or almost always ordering screening TVU or CA-125 or both). Twenty-eight percent (95% CI, 24.5% to 32.9%) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer; 65.4% (CI, 61.1% to 69.4%) did so for women at medium risk for ovarian cancer. Six percent (CI, 4.4% to 8.9%) reported routinely ordering or offering ovarian cancer screening for low-risk women, as did 24.0% (CI, 20.5% to 28.0%) for medium-risk women (P ≤ 0.001). Thirty-three percent believed TVU or CA-125 was an effective screening test. In adjusted analysis, actual and physician-perceived patient risk, patient request for ovarian cancer screening, and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations. The results are limited by their reliance on survey methods; there may be respondent-nonrespondent bias. One in 3 physicians believed that ovarian cancer screening was effective, despite evidence to the contrary. Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening, thereby exposing women to the documented risks of these tests. Centers for Disease Control and Prevention and the National Cancer Institute.
Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for ... more Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for preoperative clinical predictors, complication rates, and outcomes. Study Design. IRB approval was obtained for this retrospective analysis and chart review was performed. Results. From 268 women with early-stage (IA2 to IIA) cervical cancer, 19 (7%) had an abandoned hysterectomy for finding grossly positive lymph nodes (84%) or pelvic spread of tumor (16%). No clinical characteristics clearly identified women preoperatively at risk of having an abandoned hysterectomy. In the abandoned group, 26% suffered major morbidities, compared to 34% in the completed group (OR 0.69, [CI 0.16-2.57], P = .789). Thirty-seven percent recurred in the abandoned group, compared to 18% in the completed group (P = .168). Overall survival in the abandoned group was 73% versus 80% in the completed group (P = .772). Conclusion. The practice of abandoning a planned radical hysterectomy for unexpected metastatic disease may not worsen the outcome. of Hindawi Publishing Corporation
The purpose of this study was to develop an effective curriculum for teaching colposuspension and... more The purpose of this study was to develop an effective curriculum for teaching colposuspension and diagnostic cystoscopy. Fifty-five residents underwent an Objective Structured Assessment of Technical Skills that was composed of a task-specific checklist and validated global assessment. Thirty of the residents had been exposed to a training curriculum, and 25 residents served as untrained control subjects. For the colposuspension and cystoscopy checklists, the reliability coefficient was 0.85 and 0.72, and the interrater reliability was 0.92 and 0.68, respectively. Although residents who were provided the curriculum performed better on both task-specific checklists, the differences did not reach statistical significance. Senior residents performed consistently better than junior residents for both tasks. When a comparison was made of the junior residents separately to account for previous experience, trained residents performed significantly better on the cystoscopy checklist (P = .029). This curriculum is an effective way to teach diagnostic cystoscopy to junior residents. The checklist for this Objective Structured Assessment of Technical Skills has good reliability and construct validity.
The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of e... more The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation. In some cases, hysterectomy has been the necessary treatment to control bleeding. We report two cases of cervical pregnancy detected by ultrasound. Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques. As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained.
Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma ... more Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by m...
To study physicians' beliefs about the effectiveness of different tests for cancer screening.... more To study physicians' beliefs about the effectiveness of different tests for cancer screening. Data were examined from the Women's Health Survey of 1574 Family Medicine, Internal Medicine, and Obstetrics-Gynecology physicians to questions about their level of agreement about the clinical effectiveness of different tests for breast, cervical, ovarian, and colorectal cancer screening among average risk women. Data were weighted to the U.S. physician population based on the American Medical Association Masterfile. Multivariable logistic regression identified physician and practice characteristics significantly associated with physicians' beliefs. There were 1574 respondents, representing a 62% response rate. The majority of physicians agreed with the effectiveness of mammography for women aged 50-69years, Pap tests for women aged 21-65years, and colonoscopy for individuals aged ≥50years. A substantial proportion of physicians believed that non-recommended tests were effectiv...
Objective. The aim of this study was to determine the prevalence and types of complementary and a... more Objective. The aim of this study was to determine the prevalence and types of complementary and alternative medicine (CAM) usage by women with gynecologic cancer in an outpatient midwestern university practice.Methods. Any patient with a gynecologic cancer seen in the outpatient clinic of the gynecologic oncology division at Washington University over a 3-month period was eligible, excluding those patients with
To explore and facilitate the multifaceted process of drug development and regulatory approval in... more To explore and facilitate the multifaceted process of drug development and regulatory approval in ovarian cancer. The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO. This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of c...
Cesarean scar rupture of a gravid uterus in early gestation is rare. A 38-year-old woman, gravida... more Cesarean scar rupture of a gravid uterus in early gestation is rare. A 38-year-old woman, gravida 4, para 2-0-1-1, presented at 13 weeks' gestation with cramping and spotting. She had a history of two cesareans. Ultrasound and magnetic resonance imaging indicated probable uterine dehiscence and a viable extrauterine pregnancy. After embolization of the uterine arteries with subsequent fetal death, the subject had a hysterectomy. Intraoperatively, she had complete rupture of the lower uterine segment, but the pregnancy was enclosed within scar tissue between the uterus and bladder. Placenta percreta was found by histologic examination. Women with histories of cesareans might be at risk of early uterine rupture.
Although technical improvements have broadened the use of operative laparoscopy, the safety of th... more Although technical improvements have broadened the use of operative laparoscopy, the safety of this surgical technique in the presence of malignancy has not yet been evaluated fully. A potential complication of this procedure was highlighted in a summary of seven cases of abdominal-wall tumor implantation after laparos• copy in patients with gastrointestinal and gynecologic malignancies. 1 In addition to port-site recurrence, intra• peritoneal seeding of an otherwise localized malig• nancy may occur.
We have previously shown that objective structured assessment of technical skills performed in an... more We have previously shown that objective structured assessment of technical skills performed in an animal model was an innovative, reliable, and valid method of assessing surgical skills. Our goal was to develop a less costly bench station objective structured assessment of technical skills and to evaluate the feasibility, reliability, and validity of this exam.
Journal of Photochemistry and Photobiology B: Biology, 1992
Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which invol... more Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer.
Context Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishi... more Context Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishing these symptoms from those that normally occur in women remains problematic.
International Journal of Gynecology & Obstetrics, 1994
Platlnmn-baaed ckemotkerapy of l&k-risk stage I epithelial ovariaa cancer followiag camprehensive... more Platlnmn-baaed ckemotkerapy of l&k-risk stage I epithelial ovariaa cancer followiag camprehensive surgical staging Rubin SC.; Wong G.Y.C.; Curtin J.P.; Barakat R.R.; Hakes T.B.; Hoskins W.J. USA OBSTET GYNECOL 1993 82/l (143-147) Objective: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. Methods: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum based chemotherapy following comprehensive surgical staging.
OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemci... more OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemcitabine-carboplatin (GC) significantly improved investigator-determined progression-free survival (PFS) and objective response rate (ORR) in platinum-sensitive, recurrent ovarian cancer. To evaluate the reliability of assessment of progression and objective response per RECIST, radiologic and clinical data were assessed by an independent review committee (IRC). Radiologic images and clinical data were provided prospectively to the IRC for all randomized patients (N=484). Data were reviewed in a blinded fashion per RECIST (modified v1.0). PFS and ORR were analyzed based on the IRC assessment. Concordance between investigator- and IRC-assessed progression and objective response was assessed. The IRC analysis demonstrated a statistically significant increase in PFS (hazard ratio [HR]=0.451; 95% confidence interval [CI]=0.351 to 0.580, p<0.0001) consistent with the benefit reported by investigators (HR=0.484; 95% CI=0.388 to 0.605, p<0.0001). The concordance rate, defined by agreement on progression status, was 74.2% overall, and comparable between treatment arms (bevacizumab, 75.2% vs. placebo, 73.1%). IRC-assessed ORR was significantly improved with bevacizumab (bevacizumab, 74.8% vs. placebo, 53.7%; p<0.0001), consistent with the investigator-assessed results. The concordance rate for objective response was 79.8% overall, and comparable between treatment arms (bevacizumab, 78.9% vs. placebo, 80.6%). IRC-determined results were highly consistent with those determined by investigators, demonstrating that bevacizumab plus GC provides a significant improvement in PFS and ORR. These results suggest that investigators can reliably assess disease progression and objective response in recurrent ovarian cancer using RECIST, without the necessity of a full IRC review.
Objectives-The IL6 -174 promoter polymorphism impacts serum cytokine levels through transcription... more Objectives-The IL6 -174 promoter polymorphism impacts serum cytokine levels through transcriptional regulation. The objective of our study was to determine if -174 IL6 genotype influences survival in ovarian cancer.
ated with paclitaxel administration [5]. We now review Seven patients with gastrointestinal necro... more ated with paclitaxel administration [5]. We now review Seven patients with gastrointestinal necrosis following paclitaxel the occurrence of paclitaxel-associated bowel perforation at chemotherapy are reported. Four of seven patients had platinum the University of Washington. From 1991 to 1995 seven refractory disease, while 3/7 patients received primary paclitaxel cases of gastrointestinal necrosis have been observed in patherapy. Complications occurred 5 to 16 days following paclitaxel tients treated with paclitaxel for epithelial ovarian cancer at therapy. The most common clinical presentation was fever (7/ the University of Washington. Four of seven cases have 7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 occurred in women receiving paclitaxel for platinum refracpatients). All seven patients developed gastrointestinal necrosis tory disease. Three patients received primary paclitaxel therfollowing the first cycle of paclitaxel chemotherapy. The exact
To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gem... more To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation. Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m(2) and that of gemcitabine was 10 mg/m(2) in 3 patients, with a subsequent dose escalation of 10 mg/m(2) of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m(2) for each new cohort was used (Level 1, 10 mg/m(2) of gemcitabine and 20 mg/m(2) of cisplatin; Level 2, 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin; and Level 3, 20 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy. From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free. Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin with an acceptable tolerability profile.
To ascertain the frequency of significant pathologic alterations in prophylactic oophorectomy spe... more To ascertain the frequency of significant pathologic alterations in prophylactic oophorectomy specimens in high-risk women referred to a tertiary care center. Surgical cases for prophylactic oophorectomy referred to a gynecologic oncology clinic from November 1996 to January 2001 were reviewed. Serial sections of entirely submitted tubes and ovaries were procured and reviewed by a pathologist with expertise in gynecologic malignancies. All patients had undergone genetic counseling and either underwent mutational analysis of BRCA1 and BRCA2 genes or had family history suggestive for ovarian and breast cancer susceptibility. Thirty women with either a documented deleterious BRCA1 or BRCA2 mutation or a suggestive family history underwent prophylactic oophorectomy during the study period. Seventy-three percent of women had undergone genetic testing. Of those, 63.5% harbored a BRCA1 mutation, 13.5% were BRCA2 carriers, and the remaining 23% tested negative. Five of the 30 women (17%) were found to have clinically occult malignancy. Four of the five were diagnosed only on histologic review. A single patient had grossly apparent primary peritoneal carcinoma at the time of laparoscopy. Three patients were found to have primary fallopian tube malignancy, two with in situ papillary serous carcinoma, and one with early invasive disease. Each of the fallopian tube neoplasms measured less than 1 cm. The final patient was diagnosed with an ovarian adenofibroma with a focus of low malignant potential neoplasm and clear cell features. Three of the five were known BRCA1 mutation carriers, one had a documented BRCA2 mutation, and one has not yet been tested. The high rate of occult malignancy detected in this series suggests that this finding in women at heightened risk for ovarian cancer is relatively common. Further, clinically occult tumors were not limited to ovarian origin, and the majority of cases harbored malignant foci less than 1 cm in greatest dimension that were not recognized at the time of surgery. These findings support the recommendations that in this high-risk population (1) the fallopian tubes and ovaries should be submitted entirely and be evaluated by a pathologist with expertise in gynecologic malignancies in serial sections; (2) laparoscopy and laparotomy are the surgical modalities of choice to allow inspection of the peritoneal surfaces at time of prophylactic oophorectomy and collect fluid for cytologic evaluation; (3) despite the rarity of fallopian tube carcinoma in the general population, BRCA1 and BRCA2 mutation carriers may be at increased risk for tubal cancers.
No professional society or group recommends routine ovarian cancer screening, yet physicians&... more No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms. To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening. Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125). United States. 3200 physicians randomly sampled equally from the 2008 American Medical Association Physician Masterfile lists of family physicians, general internists, and obstetrician-gynecologists; 61.7% responded. After exclusions, 1088 respondents were included; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally. Reported nonadherence to screening recommendations (defined as sometimes or almost always ordering screening TVU or CA-125 or both). Twenty-eight percent (95% CI, 24.5% to 32.9%) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer; 65.4% (CI, 61.1% to 69.4%) did so for women at medium risk for ovarian cancer. Six percent (CI, 4.4% to 8.9%) reported routinely ordering or offering ovarian cancer screening for low-risk women, as did 24.0% (CI, 20.5% to 28.0%) for medium-risk women (P ≤ 0.001). Thirty-three percent believed TVU or CA-125 was an effective screening test. In adjusted analysis, actual and physician-perceived patient risk, patient request for ovarian cancer screening, and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations. The results are limited by their reliance on survey methods; there may be respondent-nonrespondent bias. One in 3 physicians believed that ovarian cancer screening was effective, despite evidence to the contrary. Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening, thereby exposing women to the documented risks of these tests. Centers for Disease Control and Prevention and the National Cancer Institute.
Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for ... more Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for preoperative clinical predictors, complication rates, and outcomes. Study Design. IRB approval was obtained for this retrospective analysis and chart review was performed. Results. From 268 women with early-stage (IA2 to IIA) cervical cancer, 19 (7%) had an abandoned hysterectomy for finding grossly positive lymph nodes (84%) or pelvic spread of tumor (16%). No clinical characteristics clearly identified women preoperatively at risk of having an abandoned hysterectomy. In the abandoned group, 26% suffered major morbidities, compared to 34% in the completed group (OR 0.69, [CI 0.16-2.57], P = .789). Thirty-seven percent recurred in the abandoned group, compared to 18% in the completed group (P = .168). Overall survival in the abandoned group was 73% versus 80% in the completed group (P = .772). Conclusion. The practice of abandoning a planned radical hysterectomy for unexpected metastatic disease may not worsen the outcome. of Hindawi Publishing Corporation
The purpose of this study was to develop an effective curriculum for teaching colposuspension and... more The purpose of this study was to develop an effective curriculum for teaching colposuspension and diagnostic cystoscopy. Fifty-five residents underwent an Objective Structured Assessment of Technical Skills that was composed of a task-specific checklist and validated global assessment. Thirty of the residents had been exposed to a training curriculum, and 25 residents served as untrained control subjects. For the colposuspension and cystoscopy checklists, the reliability coefficient was 0.85 and 0.72, and the interrater reliability was 0.92 and 0.68, respectively. Although residents who were provided the curriculum performed better on both task-specific checklists, the differences did not reach statistical significance. Senior residents performed consistently better than junior residents for both tasks. When a comparison was made of the junior residents separately to account for previous experience, trained residents performed significantly better on the cystoscopy checklist (P = .029). This curriculum is an effective way to teach diagnostic cystoscopy to junior residents. The checklist for this Objective Structured Assessment of Technical Skills has good reliability and construct validity.
The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of e... more The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation. In some cases, hysterectomy has been the necessary treatment to control bleeding. We report two cases of cervical pregnancy detected by ultrasound. Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques. As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained.
Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma ... more Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by m...
To study physicians' beliefs about the effectiveness of different tests for cancer screening.... more To study physicians' beliefs about the effectiveness of different tests for cancer screening. Data were examined from the Women's Health Survey of 1574 Family Medicine, Internal Medicine, and Obstetrics-Gynecology physicians to questions about their level of agreement about the clinical effectiveness of different tests for breast, cervical, ovarian, and colorectal cancer screening among average risk women. Data were weighted to the U.S. physician population based on the American Medical Association Masterfile. Multivariable logistic regression identified physician and practice characteristics significantly associated with physicians' beliefs. There were 1574 respondents, representing a 62% response rate. The majority of physicians agreed with the effectiveness of mammography for women aged 50-69years, Pap tests for women aged 21-65years, and colonoscopy for individuals aged ≥50years. A substantial proportion of physicians believed that non-recommended tests were effectiv...
Objective. The aim of this study was to determine the prevalence and types of complementary and a... more Objective. The aim of this study was to determine the prevalence and types of complementary and alternative medicine (CAM) usage by women with gynecologic cancer in an outpatient midwestern university practice.Methods. Any patient with a gynecologic cancer seen in the outpatient clinic of the gynecologic oncology division at Washington University over a 3-month period was eligible, excluding those patients with
To explore and facilitate the multifaceted process of drug development and regulatory approval in... more To explore and facilitate the multifaceted process of drug development and regulatory approval in ovarian cancer. The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO. This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of c...
Cesarean scar rupture of a gravid uterus in early gestation is rare. A 38-year-old woman, gravida... more Cesarean scar rupture of a gravid uterus in early gestation is rare. A 38-year-old woman, gravida 4, para 2-0-1-1, presented at 13 weeks' gestation with cramping and spotting. She had a history of two cesareans. Ultrasound and magnetic resonance imaging indicated probable uterine dehiscence and a viable extrauterine pregnancy. After embolization of the uterine arteries with subsequent fetal death, the subject had a hysterectomy. Intraoperatively, she had complete rupture of the lower uterine segment, but the pregnancy was enclosed within scar tissue between the uterus and bladder. Placenta percreta was found by histologic examination. Women with histories of cesareans might be at risk of early uterine rupture.
Although technical improvements have broadened the use of operative laparoscopy, the safety of th... more Although technical improvements have broadened the use of operative laparoscopy, the safety of this surgical technique in the presence of malignancy has not yet been evaluated fully. A potential complication of this procedure was highlighted in a summary of seven cases of abdominal-wall tumor implantation after laparos• copy in patients with gastrointestinal and gynecologic malignancies. 1 In addition to port-site recurrence, intra• peritoneal seeding of an otherwise localized malig• nancy may occur.
We have previously shown that objective structured assessment of technical skills performed in an... more We have previously shown that objective structured assessment of technical skills performed in an animal model was an innovative, reliable, and valid method of assessing surgical skills. Our goal was to develop a less costly bench station objective structured assessment of technical skills and to evaluate the feasibility, reliability, and validity of this exam.
Journal of Photochemistry and Photobiology B: Biology, 1992
Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which invol... more Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer.
Context Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishi... more Context Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishing these symptoms from those that normally occur in women remains problematic.
International Journal of Gynecology & Obstetrics, 1994
Platlnmn-baaed ckemotkerapy of l&k-risk stage I epithelial ovariaa cancer followiag camprehensive... more Platlnmn-baaed ckemotkerapy of l&k-risk stage I epithelial ovariaa cancer followiag camprehensive surgical staging Rubin SC.; Wong G.Y.C.; Curtin J.P.; Barakat R.R.; Hakes T.B.; Hoskins W.J. USA OBSTET GYNECOL 1993 82/l (143-147) Objective: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. Methods: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum based chemotherapy following comprehensive surgical staging.
OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemci... more OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemcitabine-carboplatin (GC) significantly improved investigator-determined progression-free survival (PFS) and objective response rate (ORR) in platinum-sensitive, recurrent ovarian cancer. To evaluate the reliability of assessment of progression and objective response per RECIST, radiologic and clinical data were assessed by an independent review committee (IRC). Radiologic images and clinical data were provided prospectively to the IRC for all randomized patients (N=484). Data were reviewed in a blinded fashion per RECIST (modified v1.0). PFS and ORR were analyzed based on the IRC assessment. Concordance between investigator- and IRC-assessed progression and objective response was assessed. The IRC analysis demonstrated a statistically significant increase in PFS (hazard ratio [HR]=0.451; 95% confidence interval [CI]=0.351 to 0.580, p<0.0001) consistent with the benefit reported by investigators (HR=0.484; 95% CI=0.388 to 0.605, p<0.0001). The concordance rate, defined by agreement on progression status, was 74.2% overall, and comparable between treatment arms (bevacizumab, 75.2% vs. placebo, 73.1%). IRC-assessed ORR was significantly improved with bevacizumab (bevacizumab, 74.8% vs. placebo, 53.7%; p<0.0001), consistent with the investigator-assessed results. The concordance rate for objective response was 79.8% overall, and comparable between treatment arms (bevacizumab, 78.9% vs. placebo, 80.6%). IRC-determined results were highly consistent with those determined by investigators, demonstrating that bevacizumab plus GC provides a significant improvement in PFS and ORR. These results suggest that investigators can reliably assess disease progression and objective response in recurrent ovarian cancer using RECIST, without the necessity of a full IRC review.
Objectives-The IL6 -174 promoter polymorphism impacts serum cytokine levels through transcription... more Objectives-The IL6 -174 promoter polymorphism impacts serum cytokine levels through transcriptional regulation. The objective of our study was to determine if -174 IL6 genotype influences survival in ovarian cancer.
ated with paclitaxel administration [5]. We now review Seven patients with gastrointestinal necro... more ated with paclitaxel administration [5]. We now review Seven patients with gastrointestinal necrosis following paclitaxel the occurrence of paclitaxel-associated bowel perforation at chemotherapy are reported. Four of seven patients had platinum the University of Washington. From 1991 to 1995 seven refractory disease, while 3/7 patients received primary paclitaxel cases of gastrointestinal necrosis have been observed in patherapy. Complications occurred 5 to 16 days following paclitaxel tients treated with paclitaxel for epithelial ovarian cancer at therapy. The most common clinical presentation was fever (7/ the University of Washington. Four of seven cases have 7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 occurred in women receiving paclitaxel for platinum refracpatients). All seven patients developed gastrointestinal necrosis tory disease. Three patients received primary paclitaxel therfollowing the first cycle of paclitaxel chemotherapy. The exact
To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gem... more To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation. Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m(2) and that of gemcitabine was 10 mg/m(2) in 3 patients, with a subsequent dose escalation of 10 mg/m(2) of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m(2) for each new cohort was used (Level 1, 10 mg/m(2) of gemcitabine and 20 mg/m(2) of cisplatin; Level 2, 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin; and Level 3, 20 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy. From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free. Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin with an acceptable tolerability profile.
To ascertain the frequency of significant pathologic alterations in prophylactic oophorectomy spe... more To ascertain the frequency of significant pathologic alterations in prophylactic oophorectomy specimens in high-risk women referred to a tertiary care center. Surgical cases for prophylactic oophorectomy referred to a gynecologic oncology clinic from November 1996 to January 2001 were reviewed. Serial sections of entirely submitted tubes and ovaries were procured and reviewed by a pathologist with expertise in gynecologic malignancies. All patients had undergone genetic counseling and either underwent mutational analysis of BRCA1 and BRCA2 genes or had family history suggestive for ovarian and breast cancer susceptibility. Thirty women with either a documented deleterious BRCA1 or BRCA2 mutation or a suggestive family history underwent prophylactic oophorectomy during the study period. Seventy-three percent of women had undergone genetic testing. Of those, 63.5% harbored a BRCA1 mutation, 13.5% were BRCA2 carriers, and the remaining 23% tested negative. Five of the 30 women (17%) were found to have clinically occult malignancy. Four of the five were diagnosed only on histologic review. A single patient had grossly apparent primary peritoneal carcinoma at the time of laparoscopy. Three patients were found to have primary fallopian tube malignancy, two with in situ papillary serous carcinoma, and one with early invasive disease. Each of the fallopian tube neoplasms measured less than 1 cm. The final patient was diagnosed with an ovarian adenofibroma with a focus of low malignant potential neoplasm and clear cell features. Three of the five were known BRCA1 mutation carriers, one had a documented BRCA2 mutation, and one has not yet been tested. The high rate of occult malignancy detected in this series suggests that this finding in women at heightened risk for ovarian cancer is relatively common. Further, clinically occult tumors were not limited to ovarian origin, and the majority of cases harbored malignant foci less than 1 cm in greatest dimension that were not recognized at the time of surgery. These findings support the recommendations that in this high-risk population (1) the fallopian tubes and ovaries should be submitted entirely and be evaluated by a pathologist with expertise in gynecologic malignancies in serial sections; (2) laparoscopy and laparotomy are the surgical modalities of choice to allow inspection of the peritoneal surfaces at time of prophylactic oophorectomy and collect fluid for cytologic evaluation; (3) despite the rarity of fallopian tube carcinoma in the general population, BRCA1 and BRCA2 mutation carriers may be at increased risk for tubal cancers.
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Papers by Barbara Goff