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Biomedical subjects

W T Creasman

Publications and source records attributed to W T Creasman.

At least 55 records · Page 3Linked to original sources

Endometrial cancer: incidence, prognostic factors, diagnosis, and treatment.

Endometrial cancer is the most common gynecologic malignancy seen in the United States. Risk factors include unopposed estrogen (both endogenous and exogenous). Since tamoxifen is said to have weak estrogen activity, it has been suggested that tamoxifen may cause endometrial cancers. Of the 15 studies reported (clinical trials, prevalence, cross-sectional, and case control), 12 showed no relationship, two noted an increased incidence of endometrial cancer, and one noted a decreased incidence. When one considers the increased incidence of endometrial cancer in breast cancer patients, potential surveillance and ascertainment bias, latency, and occult endometrial cancers, it appears that there is a very small, if any, association of tamoxifen and endometrial cancer. In the asymptomatic patient on tamoxifen, routine yearly gynecologic examinations are recommended. Special studies to evaluate the endometrium do not appear to be indicated in the asymptomatic patient.

Antineoplastic Agents, Hormonal↗

Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report.

There is a critical need to find additional effective therapies in the management of ovarian cancer. A previously reported Gynecologic Oncology Group trial demonstrated that tamoxifen is an active drug when used in the salvage setting in this malignancy. Unfortunately, this original report did not specifically examine the utility of tamoxifen in patients with clinically defined platinum-refractory disease. In this reanalysis of the results of treatment of 102 evaluable patients entered into this multi-institutional trial, an objective response rate of 13% (95% confidence interval, 6.4-22.6%) was observed in patients with cisplatin-refractory ovarian cancer. The median response duration in this patient population was 4.4 months (range 1.2-9.2 months). Although the response rate is modest, this well-tolerated hormonal agent is a reasonable therapeutic option in selected patients with ovarian cancer when salvage therapy is to be considered. A possible role for this hormonal agent in other clinical settings in ovarian cancer will need to be defined through the conduct of carefully designed randomized clinical trials.

Antineoplastic Agents, Hormonal↗

A phase II trial of prolonged oral etoposide (VP-16) as second-line therapy for advanced and recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

Prolonged oral etoposide is an active regimen in small and nonsmall cell carcinoma of the lung, carcinomas of the breast and ovary, germ cell tumors, and in lymphoma. A Phase II trial was conducted by the Gynecologic Oncology Group to determine its activity in endometrial carcinoma. Twenty-six patients with advanced or recurrent endometrial carcinoma were entered into study; one patient was ineligible because of an incorrect cell type. The remaining eligible patients were treated with etoposide at a starting dose of 50 mg/m2/day (30 mg/m2/day with prior radiotherapy) for 21 days. Based on hematologic toxicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescribed. Twenty-two patients were evaluable for response and 25 were evaluable for toxicity. Fourteen had received prior radiotherapy and 24 had received prior chemotherapy. A median of two courses were given (range, 1-10). Grade 3 or 4 leukopenia occurring in 52% was the most common complication (grade 3, 36%; grade 4, 16%). Grade 4 thrombocytopenia occurred in 16% of patients. There were no objective responses including four patients with serous papillary carcinoma. This regimen is not significantly active as second-line therapy in endometrial carcinoma.

Adenocarcinoma↗

Replacement therapy for breast cancer survivors. A pilot study.

BACKGROUND: Traditionally, breast cancer survivors were not considered as candidates for hormone replacement therapy (HRT) because of the possibility that an occult metastatic site of disease might be activated, thus negatively influencing the outcome for the patient. METHODS: A retrospective review of 77 breast cancer survivors who have taken HRT was conducted. RESULTS: Seven recurrences were reported among the 77 patients studied in-depth, with correlations to stage, age, and node and receptor status. There have been no recurrences among the 33 additional patients who were placed on the study after the completion of this analysis. CONCLUSIONS: No significant adverse outcome was detected in this group of breast cancer survivors receiving HRT. Given the established benefits of HRT, a reappraisal of this subject is necessary, and a prospective randomized trial is essential.

Adult↗

Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study.

Thirty-five patients with bulky (designated as > or = 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m2, and vincristine, 1 mg/m2, administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulocytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management.

Adenocarcinoma↗

Ovarian cancer screening.

PURPOSE: To review potential screening tools of early ovarian cancer and the associated risk factors for the development of ovarian carcinoma. DESIGN AND RESULTS: A review of pertinent literature was conducted, restricted to English-language published reports, book chapters, and articles. The value of serum tumor markers, particularly CA 125, ultrasound, transabdominal and transvaginal ultrasonography, and transvaginal color Doppler imaging as screening tools for ovarian cancer was assessed. CONCLUSION: Based on the literature, a large-scale long-term study that compares the mortality rates of a screened versus unscreened patient population is required before the efficacy of any screening method can be determined definitively.

CA-125 Antigen↗

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

Adult↗

Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases.

Electrosurgical loop conization of the cervix is a new procedure that is being rapidly accepted for treatment of cervical intraepithelial neoplasia (CIN). Concerns include fragmentation of the specimen that is frequently mandated by the size of the transformation zone and difficulty in using the largest electrosurgical loops. Two cases are presented that demonstrate the inability to accurately assign depth of invasion in cervical cancer when the focus of invasion is transfected. As a result, the patient and physician were forced to decide on whether a radical hysterectomy and pelvic lymphadenectomy were needed based on incomplete information. It is recommended that electrosurgical loop conization be confined to patients where invasive carcinoma is not expected. The use of this new technique for patients with suspected invasive carcinoma needs further evaluation.

Adult↗

Second-look laparotomy in ovarian cancer.

The role of the second-look laparotomy has become standard management in the patients with ovarian cancer without any objective evidence that it has a major impact on survival. In patients with early-stage disease, data on second-look surgery would suggest that there is very little, if any, benefit in patients who have had optimal full surgical staging and appropriate postoperative therapy. In advanced disease, even if the second-look laparotomy is negative, one-half will develop a recurrence. The role of the second-look laparotomy as a secondary debulking procedure has been suggested by some but appears to be beneficial in only a small subset of patients--less than 10%. In patients being treated on protocol, a second-look laparotomy has become the gold standard for determining effectiveness of a specific treatment being evaluated and would tend to be justified in this group to increase our knowledge and hopefully arrive at a better postsurgical therapy.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer, in which the maximum diameter of residual is < or = 1 cm, and suboptimal residual cancer, in which the residual disease is > 1 cm. Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed. This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a randomized trial of intense versus standard chemotherapy. STUDY DESIGN: Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses, respectively. There was no difference in progression-free interval or survival between the two arms. Of the 458 stage III (with residual disease > 1 cm) and stage IV patients entered in this study, 294 stage III patients comprise the current analysis. Surgical reporting forms, operation reports, and pathology reports were reviewed to determine initial greatest tumor diameter and residual tumor diameter. Patients were grouped by residual diameter. Multivariate analysis considered residual diameter of disease, age, histologic characteristics, performance status, and ascites. An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group. RESULTS: Patients ranged in age from 20 to 80 years, with a median of 60 years. All patients were Gynecologic Oncology Group performance status 0 to 2. Fifty-two percent had grade 3 tumors, and 39% and 9%, respectively, had grade 2 or 1 tumors. All patients had stage III disease. Ninety percent had serous, endometrioid, or mixed epithelial cell type tumors. Multivariate analysis revealed a relative risk of dying as follows: residual disease < 2 cm, relative risk 1.00; 2 to 2.9 cm, relative risk 1.90; 3 to 3.9 cm, relative risk 1.91; 4 to 5.9 cm, relative risk 1.74; 6 to 7.9 cm, relative risk 1.85; 8 to 9.9 cm, relative risk 2.16; > or = 10 cm, relative risk 1.82. The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant (p < 0.01). There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm. CONCLUSIONS: Among patients with suboptimal (> 1 cm residual disease) epithelial ovarian cancer, those who have small diameter residual disease (< 2 cm) tend to survive longer than those who have larger residual disease. Among those with larger residual disease, size does not affect prognosis appreciably.

Adult↗

Prognostic significance of hormone receptors in endometrial cancer.

BACKGROUND: Endometrial carcinoma is the most common female pelvic genital malignancy. Many studies suggest that approximately 75% of all endometrial cancers are clinical Stage I. More than 50% of cancer deaths are in patients with clinical Stage I disease. As a result, prognostic factors have been evaluated in an attempt to identify those patients with presumed early stage disease who will be at high risk for recurrence. Recently, hormone receptor status (estrogen [ER], progesterone [PR]) in endometrial cancer has been suggested to be a prognostic factor. METHODS: Two hundred seventeen patients with Stage I and II endometrial cancers were evaluated for cytoplasmic steroid-receptor status. These results were compared with other prognostic factors in both univariant and multivariant analysis. RESULTS: When ER and PR and combined ER/PR status were analyzed separately, patients with receptor-positive lesions had significantly better disease-free survival than those with receptor-negative lesions. The receptor status was also a significant independent prognostic factor when evaluated by stepwise proportional hazards regression analysis. CONCLUSIONS: Hormone receptor status in endometrial cancer appears to be an important prognostic factor.

Endometrial Neoplasms↗

Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study.

BACKGROUND: A clinicopathologic evaluation of clinical Stage I and II uterine sarcoma was done by the Gynecologic Oncology Group from 1979-1988. METHODS: After all eligibility criteria were met, 453 cases were evaluable and analyzed for prognostic factors. RESULTS: Of the 301 mixed mesodermal tumors (MMT), 167 were homologous (HO), and 134 were heterologous (HE). Fifty-nine tumors were leiomyosarcomas (LM). The remaining 93 sarcomas were predominantly stromal cell and adenosarcomas. For this study, only the MMT or LM tumors were analyzed. The recurrence rate for all MMT was 53% (HO, 44%; HE, 63%). The recurrence rate for LM was 71%. The site of the first recurrence included the pelvis in 21% of MMT and 14% in LM. Factors significantly related to progression-free interval (PFI) by univariate analysis among MMT were adnexal spread, lymph node metastases, tumor size, lymphatic-vascular space involvement, histologic grade, cell type, age, peritoneal cytologic findings, and depth of uterine tumor site of invasion. The prognostic factors based on multivariate analysis were adnexal spread, lymph node metastases, histologic cell type (HO versus HE), and grade of sarcoma. For LM, the mitotic index was the only factor significantly related to PFI.

Adult↗

Age as a prognostic factor in ovarian carcinoma. The Gynecologic Oncology Group experience.

BACKGROUND: The Gynecologic Oncology Group (GOG) has completed six major randomized trials in advanced ovarian carcinoma over the 15-year period between 1976 and 1990. This large database of 2123 patients provides a well-studied patient population with which to examine the importance of age as a prognostic factor. METHODS: The 2123 patients studied in the six GOG trials were analyzed as a group to determine important prognostic factors. Further analyses were then conducted to examine outcome by decade of life from younger than 40 years old to 70 years old and older and to evaluate the interaction of age with other significant prognostic variables. RESULTS: Three major prognostic factors were identified as exerting an influence on patient outcome in the overall patient population: age, volume of residual disease, and performance status. With regard to the effect of age, patients older than 69 years of age exhibited significantly poorer survival than those younger, even after correction for stage, residual disease, and performance status. This was not altered by variations in drugs, doses, and schedules; but there was no evidence that older patients tolerated intensive schedules less well than younger patients. CONCLUSIONS: Two practical conclusions result from this analysis. First, there is no evidence that modification of the drugs and schedules that make up the regimens used can overcome the adverse effect of older age. Second, age does not adversely affect the dose intensity that can be achieved; hence, age in itself is not reason to withhold or attenuate intensive chemotherapy, particularly in light of the fact that older patients have a poorer prognosis.

Adult↗

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

PURPOSE: Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS: Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS: There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION: In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

Adult↗

Adenocarcinoma of the uterine corpus.

Carcinoma of the endometrium is the most common malignancy seen in the female pelvic genital organs. Fortunately, survival is high because most patients are diagnosed in the early stage of the disease. As a result of studies identifying important prognostic factors and a significant number of patients with early clinical stage having extrauterine disease, surgical staging has been adopted for this disease entity. Knowing the exact extent of the disease allows more appropriate adjuvant therapy to be applied postoperatively. It is apparent that the patient with surgical stage I cancer needs radiation therapy only rarely, which obviously saves time and expense and reduces complications. Many patients who have been successfully treated for endometrial cancer may and should enjoy the benefits of estrogen replacement therapy without the risk of increased recurrence of their disease.

Adenocarcinoma↗