Robert C. Park

Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study.

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.

Estrogen replacement therapy following treatment for stage I endometrial carcinoma.

Abstract One hundred forty-four patients with clinical stage I endometrial adenocarcinoma were treated over an 11-year period at Madigan Army Medical Center and Brooke Army Medical Center. Following surgical staging, 44 selected patients were placed on oral estrogen replacement for a median duration of 64 months. In the estrogen user group, there were no recurrent endometrial cancer and no intercurrent death. Of the 99 nonestrogen users, there were 8 recurrences (8%) and 8 intercurrent deaths. Patients placed on estrogen replacement had low-risk factors for recurrence, namely, low tumor grade (grades 1 and 2), less than 12 myometrial invasion, and no metastases to lymph nodes or other organs. Postoperative estrogen replacement appears to be safe in selected low-risk patients.

The role of adjuvant therapy in Stage I ovarian cancer

Women with Stage I epithelial carcinoma of the ovary were initially treated by an extirpative operation and were subsequently randomized to either no further treatment, radiotherapy, or chemotherapy. Only two patients (6%) treated with chemotherapy developed recurrence, compared to five (17%) and seven (30%) patients in the no-treatment and radiotherapy regimens, respectively (P < 0.05). All patients, with the possible exception of those with Stage IA(1)g1, appeared to benefit from adjuvant chemotherapy compared to no treatment or radiotherapy.

Microinvasive carcinoma of the uterine cervix: A clinical-pathologic study☆

Abstract Of 265 patients accessioned to a study of microinvasive carcinoma of the cervix by participating institutions in the Gynecologic Oncology Group, 132 were rejected after preliminary review because of no evidence of invasion (99 patients), invasion in excess of 5 mm. (18 patients), inadequate conization (nine patients), and protocol violations (six patients). The data available for the 133 evaluable patients included clinical patient information, operative reports, narrative pathology reports, and microscopic slides. Tumor penetration was less than 2 mm. in 90 patients (67.5 per cent) and greater than 3 mm. in 21 patients (16 per cent). Lateral tumor extension was less than 4 mm. in 76 patients (57 per cent) and wider than 8 mm. in 29 patients (22 per cent). Extensive lateral spread was observed more frequently than deep penetration. Positive correlation was noted between the depth of penetration and lateral extension. Capillary-like space invasion by tumor was noted in 31 cases (23 per cent) and increased with depth of penetration. Lack of tumor differentiation occurred in patients with less than 1 mm. penetration more frequently than in those with deep penetration. A confluent pattern of tumor was observed more frequently with advanced depth of penetration and greater lateral spread. There was a strong correlation with residual tumor on hysterectomy specimen and capillary-like (CL) space involvement with deep stromal penetration and extensive lateral spread. No positive lymph nodes were observed in the 74 patients treated by radical hysterectomy and recurrence was noted in two patients with extensive CL space involvement. Conization specimens with surgical margins involved with cancer are inadequate for diagnosis of microinvasion and constitute a clear indication for management as a frankly invasive lesion. Simple hysterectomy may be the mode of therapy in patients with questionable invasion, with invasion less than 2 mm. in depth and 4 mm. in width, and without evidence of CL space invasion. Such conservative treatment is unwarranted if the conization margin is inadequate, if the margins are not clear, if invasion is deeper than 2 mm., if lateral spread is greater than 4 mm., or if tumor is present in the CL spaces.

Treatment of malignant ovarian germ cell tumors. Response to vincristine, dactinomycin, and cyclophosphamide (preliminary report)

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I‐IIA) only seven have failed. Median follow‐up for 16 patients remaining free of disease is 24.5 months. Restaging (second‐look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow‐up period for those remaining free of disease is 26.5 months. Six have had negative second‐look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease‐free. Grade 3 hematologic toxicity was seen in eight patients, dose‐limiting gastrointestinal toxicity in five patients, dose‐limiting neurotoxicity in five patients.

Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: A study of the gynecologic oncology group

Objective To determine the effectiveness and toxicity of ifosfamide chemotherapy in women with metastatic or recurrent endometrial stromal sarcomas unexposed to other chemotherapy. Methods In a prospective, multi-institutional phase II study conducted by the Gynecologic Oncology Group, the starting dose of ifosfamide was 1.5 g/m2 given daily intravenously (IV) for 5 days (reduced to 1.2 g/m2 daily in patients who had previously received radiotherapy). Mesna (2-mercaptoethane sodium sulfonate) was given IV immediatley and at 4 and 8 hours after the administration of ifosfamide. EAch dose of mesna was 20% of the total daily dose of ifosfamide. Patients were treated every 3 weeks if blood counts permitted. Therapy was discontinued if there was progression of the cancer or unacceptable toxicity. Results Twenty-two patients were entered into this study. One was excluded from analysis because of the wrong histologic type, leaving 21 evaluable for response and toxicity. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in four patients (19%), and one patient each experienced Gynecologic Oncology Group grade 4 anemia and genitourinary toxicity. Three patients experienced complete tumor responses and four had partial responses, for an overall response rate of 33.3%. Conclusion Ifosfamide is active in the therapy of women with chemotherapy-naive metastatic or recurrent endometrial stromal sarcomas.

Prognostic factors associated with radical hysterectomy failure

Two hundred seventy-five patients who underwent radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB carcinoma of the cervix between 1961 and 1982 were retrospectively analyzed to identify specific risk factors associated with treatment failure. Patients were classified as high or low risk on the basis of tumor spread to pelvic lymph nodes or surgical margins. Thirty-eight patients had tumor involvement of pelvic nodes or surgical margins. Despite postoperative whole pelvis radiation therapy in 88% of patients, 13 (34.2%) developed recurrence. All patients with involved nodes or margins who recurred died of disease. Patients with pelvic lymph node or surgical margin involvement clearly constitute a high risk group and should be considered candidates for some form of adjuvant therapy. Two hundred thirty-seven patients had negative nodes and clear surgical margins. There were 18 recurrences (7.6%) in this group. Pathologic specimens were reviewed to evaluate additional histologic criteria which might identify those patients at greatest risk for tumor recurrence in this low risk group. Patients whose tumors contained vascular-lymphatic space invasion or adenomatous histologic components recurred more frequently than patients whose tumors did not (P less than 0.05). Eighty-three percent of low risk patients who recurred had tumors with at least one of these features. Degree of differentiation and depth of invasion did not correlate with risk of recurrence. Prospective randomized trials are needed to determine the effectiveness of postoperative adjuvant therapy for patients at risk for recurrent disease.

Antibiotic Prophylaxis in Vaginal Hysterectomy: A Review

&NA; Recent experimental studies in laboratory animals have elucidated the pathogenesis of operative site infections and have defined the mechanism by which prophylactic antibiotics enhance host defenses against infection. On the basis of these experimental observations, several investigators have conducted well‐designed studies to evaluate the effectiveness of prophylactic antibiotics in reducing the risk of infection associated with vaginal hysterectomy. Without exception, these studies have demonstrated a dramatic decrease in the incidence of pelvic infections when antimicrobial agents are administered for a limited time in the perioperative period. To date, short courses of prophylactic antibiotics have not been shown to create selective pressures for the emergence of drug‐resistant organisms or to lead to the development of more serious superinfections.

Epithelial Ovarian Carcinoma of Low Malignant Potential

The records of 94 patients with epithelial ovarian carcinoma of low malignant potential were examined. These records were contributed by Walter Reed Army Medical Center, Naval Hospital, Bethesda, MD, and Naval Hospital, Portsmouth, VA. A review of microscopic sections from each of the 94 tumors confirmed that these were lesions of low malignant potential. The tumors occurred in patients of a younger age than that generally described for invasive epithelial ovarian carcinoma. Forty-seven of 94 patients had stage I disease. The corrected five- and ten-year survival rates were 95 and 87%, respectively. Adjunctive postoperative therapy may not influence survival.