[Show abstract][Hide abstract] ABSTRACT: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer.
Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS).
Forty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age=58 years (range: 21-81 years). 78% (32/41)=endometrioid histology. Stages=10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent=1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7-70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82-99%), at 3 years 90% (75-96%), and at 5 years 71% (45-86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72-94%), at 3 years 71% (51-83%), and at 5 years 64% (42-80%).
"Sandwiching" radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the feasibility and morbidity of using saline filled tissue expanders (TE) to displace the small bowel during radiation therapy in patients with gynecologic malignancies.
Ten patients undergoing surgical exploration for a gynecologic malignancy and deemed to be at high risk for the late effects of radiation therapy were consented for the possible placement of a TE. Indication for placement was need for post-operative radiation. Small bowel exclusion was reported in terms of the lowest loop identified on treatment planning film using orally ingested barium.
Small bowel loops were excluded from the pelvis to varying degrees in all patients. Lowest identifiable bowel was marked at the L4-L5 interspace in one patient, L5-S1 interspace in three patients, at or near the sacral promontory in three patients, and to the middle of S2 in one patient. In two patients the TE was removed prior to simulation. Early complications included migration of the TE during treatment, development of a vesicovaginal fistula requiring immediate removal of the TE, and enterocutaneous fistula formation in a patient who developed an abscess following treatment completion. Another patient experienced a rectovaginal fistula 18 months after removal of the TE.
TE placement can successfully isolate small bowel from the pelvis. Usage should be individualized to minimize the likelihood of short and long-term complications, particularly in patients at higher risk of morbidity.
European journal of obstetrics, gynecology, and reproductive biology 03/2009; 143(2):93-7. DOI:10.1016/j.ejogrb.2008.12.013 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide.
Women were enrolled in this multicenter, prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible patients had recurrent epithelial ovarian carcinoma with measurable disease or elevated CA 125 values. Patients had received prior platinum-based chemotherapy. Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5 of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per day and then increasing the dose as tolerated. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. The chi-square test was used to assess differences in response and toxicity, and the log-rank test was used to compare Kaplan-Meier survival curves.
The analysis included 69 women (39 women in the control arm and 30 women in the thalidomide arm). Known prognostic factors, including platinum sensitivity, were represented equally in each arm. The median thalidomide dose was 200 mg per day. The overall response rate in the control arm was 21% (complete response [CR] rate, 18%; partial response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%; PR rate, 17%) (P= .03). The median progression-free survival for the control arm was 4 months compared with 6 months in the thalidomide arm (P= .02). The median overall survival was 15 months in the control arm and 19 months in the thalidomide arm (P= .67). Toxicities were similar between groups.
The addition of thalidomide to topotecan for the treatment of recurrent ovarian cancer appears to improve response rates, and the authors believe that it warrants study through larger phase 3 trials.
Cancer 01/2008; 112(2):331-9. DOI:10.1002/cncr.23164 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient.
Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test.
Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype.
We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.
Journal of Translational Medicine 01/2006; 4(1). DOI:10.1186/1479-5876-4-6 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphatic and hematologic metastases are rare in microinvasive cervical cancers (FIGO stage IA1), supporting a role for conservative treatment. Cervical conization followed by prolonged surveillance is an accepted treatment in patients with low-risk features and negative surgical margins. This option is particularly appealing for younger or nulliparous patients, in whom fertility may be highly desired.
We report a case of a 22-year-old, HIV-negative female with stage IA1 squamous cell cervical carcinoma who was found to have bilateral lymph node metastases in both pelvic and para-aortic distributions after electing to undergo hysterectomy.
Clinicians treating patients with microinvasive cervical cancer conservatively must be aware of the possibility of lymph node involvement and should consider radiological imaging to look for metastatic disease.
[Show abstract][Hide abstract] ABSTRACT: The present review analyzes long-term survival, recurrence sites, and toxicity in women with peritoneal spread of endometrial treated with abdominal radiotherapy, in order to provide therapeutic options as a function of disease spread and histology.
Retrospective medical record review was performed of 86 patients receiving abdominal radiotherapy for endometrial carcinomas from 1975 to 1995 at the University of Minnesota.
FIGO stage distribution was 54 stage IIIA, 2 stage IIIB, 11 stage IIIC, and 19 stage IVB. Disease-free survivals were 55% at 5 years, 46% at 10 years, and 36% at 20 years. Recurrence rates were 16% for stage IIIA with one peritoneal site, 48% for stage IIIA with multiple peritoneal sites or stage IIIB or stage IIIC, and 72% for stage IVB. With univariate analysis, statistical significance was found for stage, gross peritoneal disease, nodal metastases, histology, concurrent chemotherapy, isolated adnexal spread, grade, angiolymphatic invasion, myometrial invasion, and age. Multivariate analysis found only stage, histology, and age to be significant. Most recurrences were pulmonary or peritoneal. Acute toxicity was acceptable. Six percent of patients required surgical intervention for small bowel obstructions.
Abdominal radiotherapy confers an excellent prognosis for women with stage IIIA cancers with one site of peritoneal involvement. Lack of randomized trials makes definitive treatment recommendations difficult to provide. Results are less optimal with multiple peritoneal sites of involvement, gross peritoneal spread, or papillary serous/clear cell pathology but a substantial number of such women can be cured as well.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study is evaluation of the long-term efficacy of sequential abdominopelvic radiotherapy and melphalan in the management of ovarian carcinoma.
From 1970 to 1976, 94 women with stages I-III epithelial ovarian carcinoma enrolled in a prospective nonrandomized clinical trial were prescribed 20 Gy to the upper abdomen and 50 Gy to the pelvis followed by courses of melphalan (1 mg/kg/course). Primary endpoints were survival, recurrence, and toxicity.
There were 19 stage I, 25 stage II, and 50 stage III patients. For all stages, overall survival was 42% at 5 years, 30% at 10 years, and 17% at 25 years. Median follow-up of the survivors was 24 years. Disease-free survival was 48% at 5 years and remained at 45% from 10 to 25 years. All but two recurrences occurred within the first 27 months. No recurrence or treatment-related death occurred after 8 years. No recurrence was salvaged. All but one initial recurrence was within the peritoneal cavity. Of the 31 patients undergoing a second-look surgical procedure, 84% were free of tumor. Only 8% of patients recurred after a negative second look. Stage and the presence of palpable postoperative disease were significant prognostic factors. Disease-free survivals were 95% from 5 to 25 years for stage I, 70% at 5 years and 60% at 25 years for stage II, and 20% from 5 to 25 years for stage III (P < 0.0001). Although no patient with postoperative palpable tumor was cured, 25% lived beyond 2 years. Stage III patients without postoperative palpable tumor achieved a 47% 25-year disease-free survival. Acute toxicity was acceptable, and 98% of patients completed radiation therapy. Chronic toxicity included a 12% small bowel obstruction rate and a 3% fatal second malignancy/hematological toxicity rate (two cases of acute myelocytic leukemia, one case of thrombocytopenia).
The long-term disease-free survival obtained with abdominopelvic radiotherapy followed by single alkylating agent chemotherapy has not been exceeded by three subsequent decades of multiagent chemotherapy trials. Abdominal radiotherapy may be useful to consolidate complete responses following therapy multiagent chemotherapy, particularly with the upper abdominal dose escalation provided by intensity modulated radiation therapy and possibly in conjunction with chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Endometrial stromal sarcomas (ESS) are a rare gynecologic malignancy. The optimal management of this cancer remains unclear, although previous reports have failed to demonstrate a clear benefit to adjuvant chemotherapy or radiation. With the successful application of directed biological therapy in other sarcomas, a review of the behavior and biology of this disease is warranted.
To review outcomes and patterns of failure in patients with endometrial stromal sarcoma diagnosed over 31 years at our institution and the relationship to protooncogene c-kit expression.
Hospital records and pathology were reviewed for 28 patients with endometrial stromal sarcomas [19 low-grade (LGESS) and 9 high-grade (HGESS)] treated between 1972 and 2003. Archival tissue samples from 16 patients were available and stained with CD 117 (c-kit) antibody (1:25 dilution). Staining intensity was graded 1+ to 3+ and distribution of the cellular staining as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells). Positive tumors had more than 10% of cells comprising the neoplasm display immunoreactivity. RESULTS.: We found a significant difference in 5-year overall survival between LGESS and HGESS (P = 0.001). There was no significant difference in overall survival for patients with local versus advanced disease (P = 0.53) or in overall survival for those who underwent lymphadenectomy and those who did not (P = 0.92). 50% of patients received postoperative radiation with no difference in disease-free or overall survival (P = 0.68 and P = 0.53). Ten patients relapsed (36%, four HGESS and six LGESS). Seven of sixteen (43.8%) tumor samples expressed detectable c-kit. Five of seven (71%) were HGESS, and the other two (22%) were LGESS tumors. The median survival of patients with c-kit-positive versus c-kit-negative tumors was 12 and 47 months, respectively.
This study confirms the superior overall prognosis of LGESS relative to HGESS, despite the similar rates of relapse. Although hard to assess, due to population heterogeneity and small numbers, adjuvant chemotherapy and radiation appear to be of limited benefit. Expression of c-kit was common, especially in high-grade lesions and may represent a potential therapeutic target.
[Show abstract][Hide abstract] ABSTRACT: To estimate the effect of preoperative diagnostic hysteroscopy on peritoneal cytology in patients with endometrial cancer.
A total of 256 charts were reviewed. Two cohorts were established based on diagnosis by hysteroscopy or blind endometrial sampling via either endometrial biopsy or dilatation and curettage (D&C). Malignant or suspicious peritoneal cytology was the primary outcome. Cohorts were compared using logistic regression to correct for potential confounders of stage and grade.
A total of 204 cases were diagnosed by endometrial biopsy or D&C, whereas 52 were identified by hysteroscopy. In the endometrial biopsy or D&C arm, 14 of 204 (6.9%) patients had malignant or suspicious cytology compared with 7 of 52 (13.5%) patients in the hysteroscopy arm (P = .15). After logistic regression controlling for stage and grade, the odds ratio for positive cytology after hysteroscopy was 3.88 (95% confidence interval 1.11,13.6; P = .03). Four of the 52 (7.7%) cases diagnosed by hysteroscopy were stage IIIA due to cytology alone compared with 3 of the 204 (1.4%) cases diagnosed by endometrial biopsy or D&C (P = .03).
Hysteroscopy appears to be associated with an increased rate of malignant cytology after controlling for confounders of stage and grade. Further, there appears to be an association between hysteroscopy and upstaging patients due to cytology alone.
[Show abstract][Hide abstract] ABSTRACT: To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer.
Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy.
Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2 g/m(2) over 2 h, paclitaxel 175 mg/m(2) over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath.
Combination therapy with ifosfamide 2 g/m(2), paclitaxel 175 mg/m(2), carboplatin AUC = 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.
[Show abstract][Hide abstract] ABSTRACT: Based on the reduced morbidity seen in our retrospective study, we undertook a prospective, randomized trial to determine whether transposition of the sartorius muscle improves post-operative morbidity in women with squamous cell carcinoma of the vulva undergoing inguinal-femoral lymphadenectomy.
Patients with squamous carcinoma of the vulva requiring inguinal-femoral lymphadenectomy were randomized to undergo sartorius transposition or not. All patients received perioperative antibiotics, DVT prophylaxis, and closed suction surgical site drainage. Outcomes assessed include wound cellulitis, wound breakdown, lymphocyst formation, lymphedema, and/or rehospitalization. Cohorts were compared using Fisher's exact test. Baseline characteristics were compared using Student's t test or Fischer's exact test as appropriate. Logistic regression was used to assess the impact of sartorius transposition, after adjusting for other factors.
From June 1996 to December 2002, 61 patients underwent 99 inguinal-femoral lymphadenectomies, 28 with sartorius transposition, and 33 without. The mean (SD) age for controls and patients undergoing sartorius transposition was 63.5 (15.2) and 73.8 (13.7) years, respectively (P < 0.05). There were no statistically significant differences in BSA, tobacco use, co-morbid medical conditions, past surgical history, medication use, size of incision, duration of surgery, number of positive lymph nodes, pathologic stage, pathologic grade, pre- or postoperative hemoglobin, or length of hospitalization. There were no statistically significant differences in the incidence of wound cellulitis, wound breakdown, lymphedema, or rehospitalization. The incidence of lymphocyst formation was increased in the sartorius transposition group. After adjusting for age, however, the groups appeared similar.
Sartorius transposition after inguinal-femoral lymphadenectomy does not reduce postoperative wound morbidity.
[Show abstract][Hide abstract] ABSTRACT: To assess the antitumor activity of Temozolomide, a novel alkylating agent, in patients with persistent or recurrent ovarian or primary peritoneal carcinoma who have failed other second-line chemotherapy agents. To identify the nature and degree of toxicity of Temozolomide in this group of patients.
Temozolomide was administered orally at an initial dose of 150 mg/m(2) daily for 5 days, every 4 weeks. If the initial course was tolerated without dose-limiting toxicity, then the dose was increased to 200 mg/m(2). Patients were evaluated for response and toxicity.
Fifteen patients were enrolled and evaluated. The median number of prior treatment regimens was 3. Hematologic toxicity was encountered in 26% of patients and was manageable. There were no complete or partial responses. One patient had stable disease with significant improvement in her performance status while on treatment.
This dose and schedule of Temozolomide had insignificant activity in this heavily pretreated group of patients with persistent or recurrent ovarian or primary peritoneal carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Studies in several solid tumors have shown that the presence of occult metastasis in the bone marrow or peripheral blood is highly predictive of decreased disease-free and overall survival. Our objective was to determine the incidence of circulating ovarian or primary peritoneal cancer cells in the peripheral blood at the time of disease diagnosis, or recurrence, and to determine the prognostic significance of these occult metastasis.
Peripheral blood was drawn preoperatively from 91 women thought to have newly diagnosed or recurrent epithelial ovarian or primary peritoneal carcinoma. All samples underwent a tumor-enriched immunocytochemical assay.
Sixty-four women were found to have epithelial ovarian or primary peritoneal cancer. Of the 64 women with cancer, 12 had evidence of circulating cancer cells in their peripheral blood (18.7%). Characteristics were compared between those with circulating cancer cells and those without, using Fisher's exact test or the Wilcoxon-Mann-Whitney test, as appropriate. Women with circulating cancer cells had statistically more grade 3 tumors than women without. At a mean follow-up of 18.7 months (SD 6.7 months), analysis using Kaplan-Meier estimation and the log-rank test indicated that survival curves did not differ between patients with and without circulating cancer cells.
Ovarian and primary peritoneal cancer, which historically has been thought to spread primarily by direct cell seeding throughout the abdominal cavity, can have circulating cancer cells in the peripheral blood. The clinical utility of identifying circulating cancer cells is yet to be defined.
[Show abstract][Hide abstract] ABSTRACT: Objective. Studies in several solid tumors have shown that the presence of occult metastasis in the bone marrow or peripheral blood is highly predictive of decreased disease-free and overall survival. Our objective was to determine the incidence of circulating ovarian or primary peritoneal cancer cells in the peripheral blood at the time of disease diagnosis, or recurrence, and to determine the prognostic significance of these occult metastasis. Methods. Peripheral blood was drawn preoperatively from 91 women thought to have newly diagnosed or recurrent epithelial ovarian or primary peritoneal carcinoma. All samples underwent a tumor-enriched immunocytochemical assay. Results. Sixty-four women were found to have epithelial ovarian or primary peritoneal cancer. Of the 64 women with cancer, 12 had evidence of circulating cancer cells in their peripheral blood (18.7%). Characteristics were compared between those with circulating cancer cells and those without, using Fisher's exact test or the Wilcoxon-Mann-Whitney test, as appropriate. Women with circulating cancer cells had statistically more grade 3 tumors than women without. At a mean follow-up of 18.7 months (SD 6.7 months), analysis using Kaplan-Meier estimation and the log-rank test indicated that survival curves did not differ between patients with and without circulating cancer cells. Conclusion. Ovarian and primary peritoneal cancer, which historically has been thought to spread primarily by direct cell seeding throughout the abdominal cavity, can have circulating cancer cells in the peripheral blood. The clinical utility of identifying circulating cancer cells is yet to be defined.