Jeanne M Schilder

Gynecologic Oncology Group, Buffalo, New York, United States

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Publications (38)129.47 Total impact

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    ABSTRACT: Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population.
    Gynecologic Oncology 10/2014; · 3.69 Impact Factor
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    ABSTRACT: BACKGROUND: This two-stage phase II study was designed to assess the activity of the combination of temsirolimus and bevacizumab in patients with recurrent or persistent endometrial carcinoma (EMC). METHODS: Eligible patients had persistent or recurrent EMC after receiving 1-2 prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status ≤2. Treatment consisted of bevacizumab 10mg/kg every other week and temsirolimus 25mg IV weekly until disease progression or prohibitory toxicity. Primary end points were progression-free survival (PFS) at six months and overall response rate using RECIST criteria. RESULTS: Fifty-three patients were enrolled. Forty-nine patients were eligible and evaluable. Median age was 63years, and prior treatment consisted of one or two regimens in 40 (82%) and 9 (18%), respectively. Twenty (41%) received prior radiation. Adverse events were consistent with those expected with bevacizumab and temsirolimus treatment. Two gastrointestinal-vaginal fistulas, one grade 3 epistaxis, two intestinal perforations and 1 grade 4 thrombosis/embolism were seen. Three patient deaths were possibly treatment related. Twelve patients (24.5%) experienced clinical responses (one complete and 11 partial responses), and 23 patients (46.9%) survived progression free for at least six months. Median progression-free survival (PFS) and overall survival (OS) were 5.6 and 16.9months, respectively. CONCLUSION: Combination of temsirolimus and bevacizumab is deemed active based on both objective tumor response and PFS at six months in recurrent or persistent EMC. However, this treatment regimen was associated with significant toxicity in this pretreated group. Future study will be guided by strategies to decrease toxicity and increase response rates.
    Gynecologic Oncology 12/2012; · 3.69 Impact Factor
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    ABSTRACT: OBJECTIVES: There is a lack of knowledge about the health care events experienced by individual patients that lead to a definitive diagnosis of ovarian cancer (OC). The goal of this study was to describe the various pathways and to identify an optimal path to accurate diagnosis. METHODS: Women who were referred to gynecologic oncology for a suspected OC were enrolled to this study. Medical records (MRs) from all health care providers were obtained from the time the patient recalled first suspecting a health issue through the time of diagnosis to build a decision tree model. A Monte Carlo simulation was conducted of 83,000 patients to identify the optimal pathway to reach diagnosis. RESULTS: In the Monte Carlo simulation, gynecologic oncologists and gynecologists accounted for the most efficient diagnosis in over 37.9% and 29.2% of suspected OC cases, respectively, in terms of the least amount of time to reach diagnosis. Gynecologic oncologists were further associated with the fewest health care visits needed to reach diagnosis in 37% of the simulation cases; however, 23% of trials were indifferent to any specific provider. CONCLUSIONS: The decision tree provides a more comprehensive view of the complexity in reaching an accurate diagnosis of OC. This analysis was able to identify the health care utilization patterns that underlie the events that occur to reach an accurate diagnosis in the setting of a suspected OC, and was able to identify the most efficient pathways that utilize the fewest health care resources in the least amount of time.
    Gynecologic Oncology 08/2012; · 3.69 Impact Factor
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    ABSTRACT: To determine whether clinicians at various levels of training can reproduce and apply the Morphology Index when compared to Ueland's Morphology Index data, and to determine intra-observer variability when applied by observers at various levels of training. One hundred four transvaginal ultrasound images of adnexal masses obtained at Indiana University between 1991 and 2003 were identified which had correlating surgical pathology. The images were scored by four investigators at four different levels of training. Scoring was based upon the revised University of Kentucky Morphology Index by Ueland. Each mass received 0-5 points for its structure, and 0-5 points for tumor volume. Each total score was then correlated with the surgical pathology. Sensitivity, specificity, positive predictive value and negative predictive value for each investigator were determined. All images were reviewed independently by each investigator; each was blinded to scores given by the other investigators and to final pathology. Nine malignant and 95 benign masses were noted on final pathology. Ranges for statistical values were: positive predictive value (PPV) 15-18%, negative predictive value (NPV) 93-98%, sensitivity 44-89%, and specificity 52-76%. The Morphology Index is a consistent and reliable tool for predicting benign disease demonstrating a high negative predictive value with little intra-observer variability. However, when predicting malignancy, the results showed more intra-observer variability and a positive predictive value half of that previously reported. This study confirms the clinical utility of the Morphology Index when utilized for its NPV and demonstrates its widespread application even among clinicians with minimal ultrasound training.
    Gynecologic Oncology 07/2012; 127(1):94-7. · 3.69 Impact Factor
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    ABSTRACT: Ascites in epithelial ovarian cancer (EOC) promotes tumor development by mechanisms that are incompletely understood. Lysophosphatidic acid (LPA), a major tumor-promoting factor in EOC ascites, is an enzymatic product of autotaxin (ATX) and phospholipase A(2) (PLA(2))enzymes. The contribution of PLA(2) activities to ovarian tumorigenesis was investigated. The quantitative measurement of PLA(2) activities in ascites and tissues, as well as assay conditions selective for PLA(2) subtypes, were optimized and validated. PLA(2) activities correlated with tumor-promoting activates in cell-based and in vivo assays. High activities consistent with both cytosolic and calcium-independent PLA(2) were found in human EOC ascites for the first time. Elevated PLA(2) and ATX activities were also observed in EOC compared to benign tumors and normal tissues. Cell-free and vesicle-free (S4) human EOC ascites potently promoted proliferation, migration, and invasion of human EOC cells in a PLA(2)-dependent manner. LPA mediated a significant part of the cell-stimulating effects of ascites. S4 ascites stimulated tumorigenesis/metastasis in vivo, and methyl arachidonyl fluorophosphonate was highly effective in inhibiting EOC metastasis in mouse xenograft models. PLA(2) activity was found in conditioned media from both EOC cells and macrophages. Collectively, our work implies that PLA(2) activity is a potential marker and therapeutic target in EOC.
    The FASEB Journal 07/2012; 26(8):3306-20. · 5.48 Impact Factor
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    ABSTRACT: Background The primary goal of this study was to determine the prevalence of pelvic floor symptoms in postoperative patients with endometrial cancer. The secondary goal was to assess the impact of these issues on patient quality of life.Methods This cross-sectional study looked at women (N = 25) returning for postoperative care at least 6 months after total abdominal hysterectomy for endometrial cancer. Demographic and clinical data were collected. Severity of pelvic floor symptoms was assessed using the short-form version of the Pelvic Floor Distress Inventory (PFDI-20). The impact of these symptoms on quality of life was assessed using the short-form version of the Pelvic Floor Impact Questionnaire (PFIQ-7). Demographic data and PFDI-20 and PFIQ-7 scores were summarized using descriptive statistics.ResultsPelvic symptoms were reported at a much higher rate than seen in the general public. Symptom prevalence was reported by 21/25 (84%) patients on the PFDI-20 questionnaire, with a mean score of 52.5 ± 64.8. Patients reported prevalence of symptoms in the following order: urinary symptoms (19/25 [76%]) > colorectal-anal symptoms (17/25 [68%]) > pelvic organ prolapse symptoms (11/25 [44%]). Slightly fewer than half (11/24) of the study participants reported quality of life issues associated with their pelvic symptoms, with a mean score in the mild range: 26.4 ± 64.5. The reported prevalence of the effect of pelvic symptoms on quality of life was urinary (10/25 [40%]) > colorectal-anal (8/24 [33%]) > pelvic organ prolapse (4/24 [17%]).Conclusion This study has shown that there was a high prevalence of symptoms of PFDs in our population after abdominal hysterectomy for endometrial cancer.
    Clinical Ovarian and Other Gynecologic Cancer. 06/2012; 5(1):27–30.
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    ABSTRACT: IntroductionPatient recall is often used by clinicians to create a history of care leading to consultation with a gynecologic oncologist. Although patient recall may be an efficient method to explore the context of the patient's concerns, the accuracy of recall and its potential impact on care are unknown. This study sought to explore the consistency of patient recall compared with data found in health care records.Patients and Methods This study enrolled 105 eligible patients who were referred to a gynecologic oncologist for suspected ovarian cancer. Ninety-one of these patients were interviewed regarding symptoms, health care events, and the dates leading to diagnosis. The medical records of these patients from all previous providers were obtained and data were abstracted. The intraclass correlation coefficient (intraclass correlation coefficient, ICC[3,1]) was used to examine correspondence between recall and medical record data.ResultsThere was low correspondence between patient recall and the medical record for time to diagnosis (ICC = 0.12; 95% confidence interval [CI] = −0.09 to 0.33; P = .12) and health care events (0.15; 95% CI, −0.05 to 0.348; P = .008).Conclusions There should be limited confidence in information obtained from patient recall given the inconsistency between recall and actual dates and events.
    Clinical Ovarian and Other Gynecologic Cancer. 06/2012; 5(1):17–23.
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    ABSTRACT: Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P < 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine-cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P < 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P < 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS.
    Cancer Research 05/2012; 72(9):2197-205. · 9.28 Impact Factor
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    ABSTRACT: Purpose: There are no screening or early detection tests for ovarian cancer, representing a major challenge to accurate diagnosis. The current study explored the use of capturing and analyzing health care (HC) events within the pathways followed by individual patients leading to a definitive diagnosis. Method: Women who were referred to gynecologic oncology for a suspected ovarian cancer (OC) were enrolled to this study and recalled their HC experiences in a semi-structured interview. Complete medical records (MRs) from all HC providers were obtained from the time the patient recalled suspecting a health issue through the time of diagnosis. We conducted a preliminary analysis using decision tree analysis to identify the optimal path to a rapid diagnosis incorporating both time and HC events. HC cost will be incorporated in the full model. Result: Of the 105 women who were enrolled to the study and provided medical record access, 92 eligible patients completed the interview about their experience in the HC system. Most of the HC encounters during this process were with primary care physicians (24.4%) and gynecologists (18.1%). More than 19% of patients did not report seeing a gynecologic oncologist prior to the diagnosis of ovarian cancer. The pathways originating from PCPs averaged 3.7 HC visits in 73 days prior to diagnosis (range 2-8 visits, 0-435 days). Time was significantly different between treatment pathways (p=0.003). Other common pathways averaged 2.8 visits in 62 days (for visits initiated in the emergency room or urgent care), and 3.2 visits and 64 days for care originating with a gynecologist. Women diagnosed with ovarian cancer had an average of 3.3 HC encounters over an average of 83 days whereas women with benign conditions had an average of 3.7 encounters over an average 104 days prior to diagnosis. Medical records will be used to validate patient-reported events and for additional information about tests and procedures completed. Conclusion: Although most women present to their PCPs with symptoms and concerns that ultimately lead to referral to gynecologic oncology for a suspected OC, the PCP pathway was associated with the longest time to reach diagnosis, but not with additional health care visits. Additional tasks occurring at each event (e.g. blood work, scans) will be included in the full analysis to explore the expected costs of each pathway.
    The 33rd Annual Meeting of the Society for Medical Decision Making; 10/2011
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    ABSTRACT: Tissue transglutaminase (TG2), an enzyme involved in cell proliferation, differentiation and apoptosis is overexpressed in ovarian carcinomas, where it modulates epithelial-to-mesenchymal transition (EMT) and promotes metastasis. Its regulation in ovarian cancer (OC) remains unexplored. Here, we show that transforming growth factor (TGF)-β, a cytokine involved in tumor dissemination is abundantly secreted in the OC microenvironment and induces TG2 expression and enzymatic activity. This is mediated at transcriptional level by SMADs and by TGF-β-activated kinase 1-mediated activation of the nuclear factor-κB complex. TGF-β-stimulated OC cells aggregate as spheroids, which enable peritoneal dissemination. We show that TGF-β-induced TG2 regulates EMT, formation of spheroids and OC metastasis. TG2 knock-down in OC cells decreases the number of cells harboring a cancer stem cell phenotype (CD44+/CD117+). Furthermore, CD44+/CD117+ cells isolated from human ovarian tumors express high levels of TG2. In summary, TGF-β-induced TG2 enhances ovarian tumor metastasis by inducing EMT and a cancer stem cell phenotype.
    Oncogene 10/2011; 31(20):2521-34. · 8.56 Impact Factor
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    ABSTRACT: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.
    Gynecologic Oncology 09/2011; 123(3):499-504. · 3.69 Impact Factor
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    ABSTRACT: The aim of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or peritoneal cancers. Women were enrolled on one of three dose levels of docetaxel (20, 25, or 30 mg/m(2)) administered weekly with concurrent low-dose whole abdominal radiation given as 60 cGy bid 2 days weekly for a total of 6 weeks. Thirteen women were enrolled and received 70 weekly treatments of docetaxel in combination with radiation therapy. At the first dose level, docetaxel 25mg/m(2), grade 3 fatigue and thrombocytopenia were observed. At the next dose level, docetaxel 30 mg/m(2), grade 3 febrile neutropenia, grade 4 thrombocytopenia with epistaxis, and grade 3 diarrhea were observed. Given these dose-limiting toxicities, a lower dose of docetaxel 20mg/m(2) was administered and found to be tolerable. No objective responses were observed among the 10 patients with measurable disease; however, the median progression-free survival (PFS) in all patients was 3.3 months, and 3 of the patients with measurable disease were free of tumor progression after 6 months (30%; 90% confidence interval 8.7-61%). Twice weekly low-dose whole abdomen radiation during weekly docetaxel 20 mg/m(2) was well-tolerated. Given the PFS demonstrated in these women with resistant ovarian cancer, further study of whole abdominal radiation and concurrent chemotherapy may be warranted.
    Gynecologic Oncology 11/2010; 120(2):224-8. · 3.69 Impact Factor
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    ABSTRACT: Aberrant DNA methylation is a hallmark of cancer, and DNA methyltransferase inhibitors have demonstrated clinical efficacy in hematologic malignancies. On the basis of preclinical studies indicating that hypomethylating agents can reverse platinum resistance in ovarian cancer cells, the authors conducted a phase 1 trial of low-dose decitabine combined with carboplatin in patients with recurrent, platinum-resistant ovarian cancer. Decitabine was administered intravenously daily for 5 days, before carboplatin (area under the curve, 5) on Day 8 of a 28-day cycle. By using a standard 3 + 3 dose escalation, decitabine was tested at 2 dose levels: 10 mg/m(2) (7 patients) or 20 mg/m(2) (3 patients). Peripheral blood mononuclear cells (PBMCs) and plasma collected on Days 1 (pretreatment), 5, 8, and 15 were used to assess global (LINE-1 repetitive element) and gene-specific DNA methylation. Dose-limiting toxicity (DLT) at the 20-mg/m(2) dose was grade 4 neutropenia (2 patients), and no DLTs were observed at 10 mg/m(2). The most common toxicities were nausea, allergic reactions, neutropenia, fatigue, anorexia, vomiting, and abdominal pain, the majority being grades 1-2. One complete response was observed, and 3 additional patients had stable disease for >/=6 months. LINE-1 hypomethylation on Days 8 and 15 was detected in DNA from PBMCs. Of 5 ovarian cancer-associated methylated genes, HOXA11 and BRCA1 were demethylated in plasma on Days 8 and 15. Repetitive low-dose decitabine is tolerated when combined with carboplatin in ovarian cancer patients, and demonstrates biological (ie, DNA-hypomethylating) activity, justifying further testing for clinical efficacy. Cancer 2010. (c) 2010 American Cancer Society.
    Cancer 09/2010; 116(17):4043-53. · 4.90 Impact Factor
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    ABSTRACT: Low-dose-rate (LDR) brachytherapy is an integral treatment modality in radiation oncology. Clinical efficacy is based on experience with manual source loading and continuous dose delivery. With remote afterloading technology, sources may be loaded and unloaded during the treatment course to prevent radiation exposure to nursing staff members and visitors. The aim of this study was to investigate treatment interruptions in terms of frequency and duration as well as extension of the overall treatment time period. The potential clinical impact of treatment interruptions was also considered. The treatment records of 20 patients who underwent brachytherapy in the Indiana University Department of Radiation Oncology administered with a Selectron LDR remote afterloader were reviewed. Results were tabulated and analysis performed with respect to 1) the number of interruptions, 2) delay time, 3) delay time (T(d)) as a function of total implant time (T), 4) the time of day that each interruption occurred, and 5) the time in minutes of each individual interruption. The mean number of interruptions was 44.9 per patient, (range, 24-76), with a mean prescription implantation duration of 45.7 hours and a mean actual treatment time of 51.2 hours resulting in a mean interruption time of 6.4 minutes per treatment hour. The number of interruptions was standardized and divided by the number of prescribed dose in grays, translating to 1.2 to 3.7 interruptions per gray delivered, with a mean of 1.6, resulting in an average T(d) of 11.21% (range, 7.35%-17.12%). Significant interruptions are frequent using remote afterloading LDR techniques, reducing the effective dose rate. Careful monitoring of such interruptions is warranted.
    Journal of the American College of Radiology: JACR 11/2009; 6(11):800-3.
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    ABSTRACT: No research has investigated patients' representations of the vaginal symptoms commonly experienced after cervical cancer treatment. Leventhal's Self-regulation or Common Sense Model was used to explore these representations and their relationships with quality of life after cervical cancer. Women posttreatment for cervical cancer (n = 26) from a Midwest cancer center provided information on symptom representations for their 3 most bothersome symptoms and also completed a quality-of-life scale. Women perceived vaginal symptoms as mild to moderate overall but rated approximately one-third of 11 different symptoms as severe. Symptoms identified most frequently as the most bothersome were painful intercourse (23%), decrease in sexual desire (15%), and vaginal dryness (12%). On average, symptoms were mildly distressing and acute, had a minimal effect on life, and were associated with an indeterminate degree of perceived control. Cause was attributed equally to treatment and to the cancer. Quality of life was below normed data, to a degree consistent with a minimally important difference for total well-being scores and physical, emotional, and functional well-being. Emotional and consequence representations were significantly related to quality of life. Understanding and altering symptom representations may improve quality of life for women treated for cervical cancer.
    Cancer nursing 09/2009; 32(5):378-84. · 1.88 Impact Factor
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    ABSTRACT: To estimate antitumor activity and toxicity of weekly topotecan hydrochloride in patients with persistent or recurrent cervical carcinoma who failed prior treatment. Women entered on study had or failed one prior chemotherapy regimen in addition to radiosensitizing chemotherapy, performance status less than 3, and adequate hematologic, renal, hepatic, and neurological function. Topotecan was infused at 3.0 mg/m(2) on days 1, 8, and 15 every 28 days. Twenty-seven patients were enrolled onto this study with 25 evaluable. Twenty-two patients had received radiation and chemotherapy prior to study. A median of two and mean of three courses of chemotherapy was given (range, one to eight courses). The most frequently severe adverse events were grade 3 anemia (28%) and grade 4 (4%) along with grade 3 neutropenia (8%) and grade 4 (8%). Two patients had grade 4 thrombocytopenia. There were no complete or partial responders. Ten patients (40%) had stable disease, twelve (48%) had increasing disease, and response could not be assessed in three (12%). The median progression-free survival was 2.4 months for the patients with increasing disease and 6.2 months (3.5-8.8 months) for those with stable disease. Disease location was equally divided within and outside the irradiated field. The 12 patients with increasing disease were more likely to have disease outside the pelvic radiation field. There were no complete or partial responders to weekly topotecan among the 25 patients in this study.
    Gynecologic Oncology 09/2009; 115(2):285-9. · 3.69 Impact Factor
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    ABSTRACT: 2-Methoxyestradiol (Panzem, 2ME2) is an endogenous metabolite of estradiol that destabilizes microtubules and exerts anti-angiogenic properties. This study was conducted to determine the activity and safety of 2ME2 administered as a NanoCrystal dispersion (NCD) formulation in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Eligible patients had relapsed, platinum-resistant or refractory EOC with measurable or detectable disease. There was no limit on the number of prior treatment regimens. 2ME2 NCD 1000 mg orally four times daily (q.i.d.) was administered continuously during 4 week cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints were assessment of toxicity, rate of clinical benefit defined as the number of patients experiencing an objective response, a CA125 response or stable disease (SD) >3 months, mean change in CA-125, progression-free survival (PFS), and pharmacokinetic analyses of 2ME2. Eighteen patients were enrolled. Median age was 65.5 (range 40-73). Patients had received a median of five prior treatments. The most common adverse events were fatigue (78%), nausea (78%), diarrhea (39%), neuropathy (50%), edema (39%), and dyspnea (44%), the majority being grade 1-2. There were no objective responses, but seven patients had SD as best response. Of those, two patients had SD for greater than 12 months. The rate of clinical benefit was 31.3%. Fairly stable plasma levels of 2ME2 ranging within the predicted therapeutic window were observed. The NCD formulation of 2ME2 is well tolerated in patients with heavily pretreated EOC. Few of these heavily pretreated patients had sustained stable disease.
    Gynecologic Oncology 08/2009; 115(1):90-6. · 3.69 Impact Factor
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    ABSTRACT: To review our institutional experience in the treatment of primary vaginal cancer and identify predictors for outcome, in particular, recurrence rate. We retrospectively reviewed the charts of 45 patients identified as having primary squamous cell cancer and adenocarcinoma of the vagina and recorded information regarding both patient and tumor characteristics and treatment modalities. Treatment modalities included surgery and radiation with or without chemotherapy (6 patients), radiation alone (30 patients), and chemoradiation (9 patients). Then, univariate and multivariate analyses were used to identify factors, which predicted for recurrence. Kaplan-Meier survival curves were also generated. The median follow-up time for all surviving patients was 5.8 years (range, 9-146 months). The mean and the median minimum tumor doses were 7300 cGy. The 5-year overall survival rate was 71%, and the 5-year progression-free survival rate was 77%. The 5-year overall survival rates by stage were carcinoma in situ with microinvasion and stage I, 92%; stage II, 82%; and stages III and IVA, 20% (P = 0.0005). The 5-year progression-free survival rates by stage were carcinoma in situ and stage I, 92%; stage II, 88%; and stages III and IVA, 30% (P = 0.00049). Of the factors analyzed, only stage predicted for a statistically significant increased risk for recurrence (P = 2.23E-0.05). Early-stage vaginal cancer can be successfully managed with radiation therapy with excellent rates of local control and survival. Patients with stages III and IV disease have a very poor outcome, and more aggressive therapies need to be investigated. Given the limited number of patients treated with chemotherapy and radiation, no definitive conclusions can be made regarding the impact of combined therapy in the management of this disease.
    International Journal of Gynecological Cancer 06/2009; 19(4):686-93. · 1.94 Impact Factor
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    ABSTRACT: Ovarian tumors frequently express c-Kit and/or platelet-derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Eligible patients had recurrent, platinum-resistant, or refractory EOC that expressed PDGFRalpha or c-kit, as determined by immunohistochemistry. Imatinib mesylate at a dose of 600 mg orally once daily was administered continuously with docetaxel at a dose of 30 mg/m(2) given intravenously once weekly in Weeks 1 through 4 of every 6-week cycle. The primary endpoint was objective response rate (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Thirty-four patients were screened for PDGFRalpha and c-kit expression to enroll 23 patients between December 2003 and October 2005. Four patients had c-kit-positive/PDGFR-negative tumors, 11 patients had PDGFR-positive/c-kit-negative tumors, and 8 patients had c-kit-positive/PDGFR-positive tumors. The median patient age was 56 years (range, 33-76 years). Patients had received a median of 3 prior treatments. The ORR was 21.7% and included 1 complete and 4 partial responses. An additional 3 patients had stable disease for more than 4 months. Expression of PDGFR, c-kit, phosphatase and tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict response to therapy. The most common adverse events encountered were fatigue (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the majority of those events were graded as grade 1 or 2. The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c-kit or PDGFRalpha. Few patients had sustained responses or stable disease.
    Cancer 08/2008; 113(4):723-32. · 4.90 Impact Factor
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    ABSTRACT: The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown to derive from tissue stem cells. To affirm the existence of OCICs, xenoengraftment of as few as 100 dissociated spheroid cells allowed full recapitulation of the original tumor (grade 2/grade 3 serous adenocarcinoma), whereas >10(5) unselected cells remained nontumorigenic. Stemness properties of OCICs (under stem cell-selective conditions) were further established by cell proliferation assays and reverse transcription-PCR, demonstrating enhanced chemoresistance to the ovarian cancer chemotherapeutics cisplatin or paclitaxel and up-regulation of stem cell markers (Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4) compared with parental tumor cells or OCICs under differentiating conditions. To identify an OCIC cell surface phenotype, spheroid immunostaining showed significant up-regulation of the hyaluronate receptor CD44 and stem cell factor receptor CD117 (c-kit), a tyrosine kinase oncoprotein. Similar to sphere-forming OCICs, injection of only 100 CD44(+)CD117(+) cells could also serially propagate their original tumors, whereas 10(5) CD44(-)CD117(-) cells remained nontumorigenic. Based on these findings, we assert that epithelial ovarian cancers derive from a subpopulation of CD44(+)CD117(+) cells, thus representing a possible therapeutic target for this devastating disease.
    Cancer Research 06/2008; 68(11):4311-20. · 9.28 Impact Factor

Publication Stats

961 Citations
129.47 Total Impact Points

Institutions

  • 2012
    • Gynecologic Oncology Group
      Buffalo, New York, United States
    • Indiana University Health
      Bloomington, Indiana, United States
  • 2009
    • Sarasota Memorial Health Care System
      Sarasota, Florida, United States
  • 1997–2007
    • Indiana University-Purdue University Indianapolis
      • • Department of Obstetrics and Gynecology
      • • Department of Radiology
      Indianapolis, Indiana, United States
  • 1999
    • Indiana University-Purdue University School of Medicine
      • Obstetrics and Gynecology
      Indianapolis, Indiana, United States