Rodrique Mortel

Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study).

Analysis of 588 patients with vulvar carcinoma delineated four risk groups by the proportional hazards model. Groin node status (laterality and number positive) and lesion diameter were the only two important independent prognostic factors. The 5-year relative survival rates were 98%, 87%, 75%, and 29% for the risk group categories of minimal (negative groin nodes and lesion diameter less than or equal to 2 cm), low (one positive groin node and lesion diameter less than or equal to 2 cm or negative groin nodes and fewer than two lesions less than or equal to 8 cm diameter), intermediate (negative groin nodes and lesion diameter greater than 8 cm diameter, one positive groin node and lesion diameter greater than 2 cm, or two unilaterally positive groin nodes and lesion diameter less than or equal to 8 cm), and high (three or more positive groin nodes or two bilaterally positive groin nodes), respectively. Applying the International Federation of Gynecology and Obstetrics staging (1988) to these data discriminated risk of death (caused by recurrent vulvar cancer); the 5-year rates were 98%, 85%, 74%, and 31% for stages I, II, III, and IV, respectively. However, within International Federation of Gynecology and Obstetrics stage III there were 47 low-, 95 intermediate-, and 28 high-risk patients with relative survivals of 95%, 74%, and 34%, respectively. Overall, this assessment validates current International Federation of Gynecology and Obstetrics vulvar carcinoma staging, but further refinements are warranted in stage III.

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses. Discrimination of benign from malignant disease

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Adjuvant progestogen therapy in the primary definitive treatment of endometrial cancer

Abstract On the basis of reported successful hormone therapy for recurrent cancer of the endometrium, a multi-institutional program was established in 1963 and terminated in 1968 to study the adjuvant use of a progestogen in the primary definitive treatment of uterine carcinoma. The research protocol restricted entry to patients with disease limited to the uterine corpus as established by clinical evaluation, surgery, and pathology. Option of surgery alone or surgery plus irradiation was permitted. Depo-Provera and placebo given over 14 wk were randomly assigned in such a way that 285 patients received hormone; 287 served as controls. Survival analysis at 4 yr indicated no significant contribution to results by the adjuvant therapy. Overall excellent survival for treated patients and controls appeared to be the result of the high degree of patient selection incorporated in the protocol design. The influence of patient selection and of variations of disease-related parameters upon the results is discussed especially as it may affect future programs dealing with comparable patient material.

A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix: A preliminary report of a Gynecologic Oncology Group Study☆

Between June 1981 and December 1985, 296 evaluable patients with carcinoma of the cervix (stages IIB, III, or IVA) were randomized to radiation therapy and either hydroxyurea (139 patients) or misonidazole (157 patients). All patients had undergone clinical, radiographic, and surgical staging. Patients with metastasis to periaortic nodes were ineligible for study. Patients received external radiation therapy to the pelvis and either one or two intracavitary applications. Hydroxyurea was given in a dose of 80 mg/kg each Monday and Thursday during external radiation therapy. Misonidazole was given in a dose of 1 gm/m2 in the same schedule, not to exceed 12 gm/m2. Of the evaluable patients, 60.8% had stage IIB disease and 33.8% had stage IIIB disease. Negative pelvic lymph nodes were found in 79.2% of the patients. Median age was 49 years (first and third quartiles 40 and 60, respectively). There were 51 patients who had severe and 15 patients who had life-threatening adverse effects (including two treatment-related deaths). As of February 1987 half the patients have either failed or been followed-up for at least 43 months. The group treated with hydroxyurea had a longer progression-free interval, bordering on statistical significance, than those treated with misonidazole (p = 0.08). The median progression-free interval for all patients randomized to hydroxyurea is 42.9 months and for misonidazole it is 40.4 months. The median progression-free interval for patients with stage III and IV disease who received hydroxyurea has not been reached and for the misonidazole group it was 10.1 months. There have been 120 recurrences, 51 (36.7%) in the hydroxyurea group and 69 (43.9%) in the misonidazole group; 51.7% of the recurrences have been limited to the pelvis or vagina. Failure limited to the pelvis occurred in 18.0% of patients receiving hydroxyurea and 23.6% of patients receiving misonidazole. There were 108 deaths, 47 (33.8%) in the hydroxyurea group and 61 (38.9%) in the misonidazole group; survival does not differ statistically between the two regimens at this point in follow-up (p = 0.25). Hydroxyurea has more short-term gastrointestinal and marrow toxicity, but is free of long-term neurotoxicity. Preliminary analyses indicate that there is no role for radiation therapy with misonidazole in cervical carcinoma.

Endometrial cancer. Therapeutic decision and the staging process in “early” disease

An all inclusive, widely accepted system for correlation of indices of pathophysiology in endometrial cancer with a spectrum of therapeutic management has yet to be developed. Improved understanding of tumor growth should lead to more logical, individualized treatment especially in terms of irradiation. To support these philosophies a brief review of past reports and studies, especially the Endometrial Adjuvant Study is provided. From an analysis of 574 patients in this study, it is apparent that prognostic factors could be separated as major, differentiation, and tumor penetration and minor, number of capsules of radium and depth of uterus. A pilot study under the Gynecologic Oncology Group suggests the correlation of the major factors with lymph node involvement. Since depth of penetration and lymph node involvement are most accurately determined by surgery and pathology, surgical staging is suggested as a guide for therapeutic decision.

Urinary polyamine levels in patients with localized malignancy.

Polyamine levels (putrescine, spermidine, and spermine) were determined in 24‐hour urine samples by a high voltage electrophoresis technique. Twentyfour of 26 patients with localized malignant tumors had two or more elevated urinary polyamine levels. Seven of 12 patients with regional spread of their cancer and five of 11 patients with localized benign and/or noninvasive tumors had elevated urinary polyamine levels. Elevations were seen more frequently in patients with genitourinary, gastrointestinal, and pulmonary tumors and less frequently in patients with gynecologic tumors. Our data suggest that there is no significant difference between the individual or total polyamine levels obtained in patients with localized malignant tumors, and those levels obtained in patients previously studied with widespread metastatic disease.

The role of prostaglandins in the excessive nausea and vomiting after intravascular cis-platinum therapy

Abstract Ten patients had serial evaluations of plasma prostaglandin E 2 , prostaglandin 2α , and 6-keto-PG 1α during administration of cis -platinum chemotherapy. No significant changes were noted in PGF 2α and 6-keto-PGF 1α whereas PGE 2 showed a decrease. This would indicate that the nausea and vomiting of platinum therapy is not a result of tumor release of prostaglandins. All patients had known residual cancer and all had elevated levels of PGE 2 and 6-keto-PGF 1α .

The role of adjunctive radiotherapy for stage I endometrial carcinoma: preoperative vs postoperative irradiation.

Abstract Eighty-five patients with clinical Stage I endometrial carcinoma were reviewed: 81% of patients had either pre-operative or post-operative radiotherapy (RT). The incidence of deep myometrial invasion (outer 13 of thickness) of pre-op RT vs. post-op RT group was 6% and 28% respectively; the pre-op irradiation seemed to alter the depth of myometrial invasion. Eleven patients (13%) developed recurrences: 9 of these patients (82%) had recurrences in the extrapelvis. The incidence of extrapelvic recurrence of patients with Grade 3 tumors was 29% (414); those with deep myometrial invasion was 33% (412). The overall 5 year survival and complication rate was 89% and 4% respectively: these results were comparable between pre-op RT and post-op RT groups. However, post-op RT offers the advantage of accurate surgical-pathologic staging and optimal individualization of adjuvant therapy. In addition, those who have deep myometrial invasion and/or Grade 3 tumors may require systemic therapy in view of high incidence of distant failures.

Stage I B glassy cell carcinoma of the cervix with ovarian metastases

Abstract A patient with stage IB glassy cell carcinoma of the uterine cervix and ovarian metastases is described. The aggressive nature of this tumor necessitates its histologic and clinical distinction from other forms of cervical carcinoma. Ovarian conservation at the time of radical surgery for this type of cervical carcinoma may not be advisable.

Aminothiadiazole (NSC #4728) in patients with advanced cervical carcinoma. A phase II study of the Gynecologic Oncology Group.

Twenty-one evaluable patients with advanced squamous-cell cervical cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Nineteen had prior chemotherapy. One patient had a partial response; six had stable disease; 14 had increasing disease; and two were inevaluable for response. There was a single life-threatening toxic episode. Aminothiadiazole used in this dosage and schedule has minimal activity in previously treated cervical carcinoma patients.