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Biomedical subjects

E L Trimble

Publications and source records attributed to E L Trimble.

At least 19 recordsLinked to original sources
PubMed2001

Extended surgical staging for uterine papillary serous carcinoma: survival outcome of locoregional (Stage I-III) disease.

OBJECTIVE: The aim of this study was to evaluate survival outcome in patients with locoregional uterine papillary serous carcinoma (UPSC) after extended surgical staging (ESS). METHODS: All patients diagnosed with FIGO Stage I-III UPSC undergoing ESS (vertical incision, peritoneal cytology, TAH/BSO, omental biopsy, lymph node sampling, peritoneal biopsy) between 1/1/89 and 12/31/98 were identified retrospectively from the tumor registry database. Pathologic features predictive of regional extrauterine spread were evaluated using the log-rank test. The Kaplan-Meier method was used to generate survival curves, and median survival determinations were compared using the log-rank test or the proportional hazards regression model. RESULTS: Twenty-six patients with locoregional UPSC were identified: FIGO Stage I (n = 11), Stage II (n = 7), and Stage III (n = 8). The median age at diagnosis was 66 years. Preoperative endometrial pathology correctly identified the presence of UPSC in 76.9% of cases. The only pathologic feature found to be predictive of regional extrauterine spread (Stage III) was myometrial invasion > or =50% (P = 0.028). Adjuvant radiation therapy (RT) was administered to 6/18 patients with Stage I/II disease and 5/8 patients with Stage III disease. Platinum-based chemotherapy was administered to 5 patients with Stage III disease. All recurrences of Stage I/II disease were located within the pelvis (16.7%). For Stage III disease, all recurrences occurred at distant sites (42.9%). The median follow-up time for surviving patients was 39.0 months (mean = 45.0 months). For all patients, the overall 5-year survival rate was 61.2%. According to FIGO stage, the overall 5-year survival rates were Stage I, 81.8%; Stage II, 64.3%; and Stage III, 31.3%. No significant differences were detected in the risk of death by stage, although there was a trend toward worse survival with Stage III disease: Stage I hazard ratio [HR] = 1.00, Stage II HR = 1.68, 95% confidence interval [CI] = 0.23-12.03, Stage III HR = 3.63, 95% CI = 0.65-20.12. CONCLUSIONS: Patients with locoregional UPSC following ESS have a more favorable prognosis than previously thought. The additional information provided by ESS facilitates the selection of adjuvant therapy. Whole pelvic RT is recommended for patients with Stage I/II disease. Pathologic Stage III disease portends a significant risk of distant recurrence. For these patients, administration of adjuvant chemotherapy should be considered in addition to directed RT.

Aged↗
PubMed2001

Ovarian tumors of low malignant potential.

Ovarian tumors of low malignant potential (LMP) differ from epithelial ovarian carcinoma in etiology, molecular biology, and prognosis. LMP tumors are not precursor lesions to ovarian carcinoma. Treatment is primarily surgical. Women found to have an ovarian tumor of LMP should undergo removal of the involved adnexa; surgical staging; and cytoreductive surgery. Women in the reproductive years should be given the option of conservative surgery, preserving the contralateral adnexa and uterus. There is no proven benefit to adjuvant chemotherapy or radiotherapy after primary surgery. In most cases, the diagnosis of an ovarian tumor of LMP conveys good prognosis, with excellent long-term survival.

Female↗
PubMed2001

Treatment of platinum-resistant ovarian cancer.

In the United States, almost 70% of the 23,000 women diagnosed annually with epithelial ovarian cancer present with advanced disease (FIGO stages III-IV). Primary therapy for these patients includes surgical cytoreduction and 6-8 courses of platinum- and taxane-based chemotherapy. Although 90% of patients will respond to this multi-modality combination regimen, most patients will experience recurrences. The 5 year survival for women with stage III disease is 15-30% and 0-20% for those with stage IV disease. Medical and gynecological oncologists, therefore, must be prepared to treat many women with recurrent ovarian cancer.

Animals↗
PubMed2000

A model for predicting surgical outcome in patients with advanced ovarian carcinoma using computed tomography.

BACKGROUND: A reliable model for predicting the outcome of primary cytoreductive surgery may be a useful tool in the clinical management of patients with advanced epithelial ovarian carcinoma. METHODS: Forty-one women with a preoperative computed tomographic (CT) scan of the abdomen and pelvis and a histologic diagnosis of Stage III or IV epithelial ovarian carcinoma following primary surgery performed by one of nine gynecologic oncologists were identified from tumor registry databases. All CT scans were analyzed retrospectively using a panel of 25 radiographic features without knowledge of the operative findings. Patient demographics, surgical findings and outcome, Gynecologic Oncology Group performance status, and pre-operative serum CA125 values were collected from patient medical records. Residual disease measuring < or = 1 cm in maximal diameter was considered an optimal surgical result. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each radiographic feature and clinical characteristic. Based on statistical probability of each factor predicting cytoreductive outcome, 13 radiographic features, in addition to performance status, were selected for inclusion in the final model. Each parameter was assigned a numeric value based on the strength of statistical association, and a total Predictive Index score was tabulated for each patient. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to predict surgical outcome. Statistical significance was evaluated using the Fisher exact test. RESULTS: Twenty of 41 patients (48.8%) underwent optimal cytoreduction to </= 1 cm residual disease. CT features of peritoneal thickening, peritoneal implants (>/= 2 cm), bowel mesentery involvement (>/= 2 cm), suprarenal paraaortic lymph nodes (>/= 1 cm), omental extension (spleen, stomach, or lesser sac), and pelvic sidewall involvement and/or hydroureter were most strongly associated with surgical outcome. Using the Predictive Index scores, a receiver operating characteristic curve was generated with an area under the curve = 0. 969 +/- 0.023. In the final model, a Predictive Index score >/= 4 had the highest overall accuracy at 92.7% and identified patients undergoing suboptimal surgery with a sensitivity of 100% (21/21). The specificity, or ability to identify patients undergoing optimal surgery, was 85.0% (17/20). The PPV of a Predictive Index score >/= 4 was 87.5% (21/24), and the NPV was 100%. The ability of this model to correctly predict surgical outcome was statistically significant (P < 0.001). CONCLUSIONS: In this model, a Predictive Index score >/= 4 demonstrated high sensitivity, specificity, PPV, and NPV, and was highly accurate in identifying patients with advanced epithelial ovarian carcinoma unlikely to undergo optimal primary cytoreductive surgery. The Predictive Index model may have clinical utility in guiding the management of patients with ovarian carcinoma.

Adult↗
PubMed2000

Saving the lymph nodes.

We need improved imaging and staging techniques to identify metastatic disease in the lymph nodes. Once we are able to do this accurately, then we can save the lymph nodes. Until that time, however, gynecologic oncologists should give careful thought as to which nodes they choose to remove and how lymph node removal may affect short-term and long-term morbidity.

Female↗
PubMed2000

Innovative therapies for advanced ovarian cancer.

The emergence of drug-resistant tumors during therapy for ovarian cancer remains an obstacle to improving long-term outcomes. Active areas of ovarian cancer research include clinical evaluation of non-cross-resistant antineoplastic agents that demonstrated single-agent activity in ovarian cancer during the 1990s: oxaliplatin, the new anthracyclines (epirubicin, liposomal doxorubicin), topotecan, oral etoposide, gemcitabine, and vinorelbine. Most of these new agents are currently being evaluated as a component of doublet and triplet combination regimens for advanced ovarian cancer, with use of sequential alternating doublet regimens gaining interest. The potential role of intraperitoneal therapy continues to be investigated. In addition, there are a variety of innovative treatment strategies on the horizon that are targeted at underlying disease processes, including anticancer vaccines, gene therapy, and antiangiogenic therapy. Based on this multitude of investigational questions and the low cure rates currently achieved, all women with advanced ovarian cancer should be offered participation in clinical trials.

Angiogenesis Inhibitors↗
PubMed1999

SEER data, corpus uteri cancer: treatment trends versus survival for FIGO stage II, 1988-1994.

OBJECTIVE: 1998 Surveillance, Epidemiology, and End Results (SEER) data estimate an 83.1% 5-year survival rate for corpus uteri adenocarcinoma FIGO stage II. The SEER data were evaluated to determine whether primary treatment differences using simple hysterectomy or radical hysterectomy, with or without radiation, altered disease survival. MATERIALS AND METHODS: SEER incidence data for FIGO II uterine corpus cancer of adenocarcinoma histology from 1988 to 1994 were stratified by hysterectomy type (simple versus radical) and whether radiation was given. Survival rates were calculated using a relative survival method and are expressed as percentages. Statistical analysis was done using a Z test. RESULTS: The 5-year cumulative survival rate for patients with stage II uterine corpus adenocarcinoma who received surgery alone as primary therapy was 84.36% with simple hysterectomy and 92.96% with radical hysterectomy (P<0.05). Survival for patients who received combination radiation and surgery as primary therapy was 82.77% with simple hysterectomy and 88.02% with radical hysterectomy (P<0.05). Pelvic and para-aortic nodes were negative. There was no significant survival difference for radiation versus no radiation in either surgical group. CONCLUSION: Radical hysterectomy is associated with better survival when compared to simple hysterectomy for FIGO II corpus uteri adenocarcinoma.

Adenocarcinoma↗
PubMed1999

A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high-dose carboplatin as primary treatment of patients with small-volume residual ovarian cancer.

PURPOSE: Because intraperitoneal (i.p.) therapy may provide a therapeutic advantage and because hyperthermia enhances carboplatin (CBDCA) cytotoxicity, we evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via continuous hyperthermic peritoneal perfusion (CHPP) in patients with small-volume residual ovarian cancer. PATIENTS AND METHODS: Six patients underwent optimal cytoreductive procedures (residual disease < or =5 mm) as initial treatment of stages II and III epithelial ovarian adenocarcinoma. All patients received a 90-min CHPP at a CBDCA dose of 800-1200 mg/m2, with the perfusate being recirculated rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures of 41-43 degrees C. Plasma, perfusate, and urine samples were collected and platinum was quantified by flameless atomic absorption spectrophotometry. RESULTS: At no time did any patient's core temperature exceed 40 degrees C. Peak perfusate platinum concentrations were 8- to 15-fold higher than peak ultrafilterable plasma concentrations. The permeability-area product was extremely high and variable (14-90 ml/min), resulting in a regional advantage of 1.9-5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose-limiting hematologic toxicity was observed at a dose of 1200 mg/m2 and this was associated with a CBDCA AUC in plasma of 11 mg min ml(-1). CONCLUSION: CHPP with CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose-limiting hematologic toxicities observed at 1200 mg/m2, correlated with the plasma CBDCA exposure established when lower doses of CBDCA are given systemically. The pharmacokinetic data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area. Variable drug absorption and clearance make the prediction of systemic exposure highly uncertain. These findings may have important implications for novel therapies given i.p.

Adenocarcinoma↗
PubMed1999

Dose-intensive approaches to ovarian cancer.

Increasing the total dose or the dose intensity of platinum does not improve survival in women with ovarian cancer. High-dose chemotherapy with hematologic support has not been shown to be more effective than standard-dose chemotherapy. Regional dose intensity, through intraperitoneal chemotherapy, may have a role in the treatment of advanced ovarian cancer. Further studies are needed to identify the optimal combination of agents, in addition to a platinum and a taxane, to be used in primary therapy for ovarian cancer.

Anthracyclines↗
PubMed1998

Lymph node sampling and survival in endometrial cancer.

OBJECTIVE: To determine the impact of pelvic lymph node sampling on survival in women with FIGO stage I and II endometrial adenocarcinoma. METHODS: We reviewed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program on 9185 women with stage I endometrial cancer and 881 women with stage II endometrial cancer. Life table analysis was used to compare survival rates. RESULTS: Overall, lymph node sampling did not appear to convey survival benefit. The 5-year relative survival for 6363 women with stage I endometrial cancer who did not undergo lymph node sampling was 0.98, compared to 0.96 for 2831 women who did undergo lymph node sampling at the time of hysterectomy, a nonsignificant difference. Lymph node sampling (LNS) was associated with increased survival among those with stage I, grade 3 disease, but not grade 1 or grade 2. Women with stage I, grade 3 disease who underwent LNS had a relative 5-year survival of 0.89, compared to 0.81 for those who did not undergo LNS (P = 0.0110). Nonsignificantly improved survival associated with LNS for women with grade 3 disease was observed in International Federation of Gynecology and Obstetrics stages Ib, Ic, and II. CONCLUSIONS: The observed survival benefit associated with lymph node sampling may be due to identification of women with more advanced endometrial cancer. Accurate determination of grade and extent of tumor is necessary to delineate which patients may benefit from lymph node sampling at hysterectomy. Effective cooperation between surgical pathology and gynecology services may be required to ensure adequate examination of the hysterectomy specimen. A surgeon with expertise in performing lymph node sampling should be available if operative findings render lymph node sampling appropriate.

Adenocarcinoma↗
PubMed1998

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7.

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.

Adult↗
PubMed1997

Patterns of care for women with ovarian cancer in the United States.

PURPOSE: To characterize treatments for ovarian cancer, to determine if recommended staging and treatment were provided, and to determine factors that influence receipt of recommended staging and treatment. METHODS: A total of 785 women diagnosed with ovarian cancer in 1991 were selected from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Type and receipt of recommended staging and treatment were examined using data on surgery and physician-verified chemotherapy. RESULTS: Most women with presumptive stage I and II ovarian cancer were treated with surgery alone (58%), while women with stage III or IV disease were treated with surgery plus platinum-based chemotherapy (75% stage III, 56% stage IV). Approximately 10% of women with presumptive stage I and II, 71% with stage III, and 53% with stage IV disease received recommended staging and treatment. The absence of lymphadenectomy and assignment of histologic grade were the primary reasons women with presumptive stage I and II cancer did not receive recommended staging and treatment, whereas for stages III and IV, it was due to older women not receiving surgery plus platinum-based adjuvant chemotherapy. Age, stage, comorbidity, "other" race/ethnicity, and treatment at a facility with an approved residency training program were associated with whether recommended staging and therapy were received. CONCLUSION: Older women with late-stage disease did not receive recommended treatment. The majority of women with early-stage disease did not receive recommended staging and treatment.

Adolescent↗