Jackson B. Beecham

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.

Granulosa cell tumors of the ovary. A clinicopathological study of 118 cases with long-term follow-up

Abstract A retrospective study of 118 cases of granulosa cell tumor of the ovary with a follow-up from 5 to more than 30 years was made. Abnormal bleeding before, during, or after the menopause was the most common presenting symptom. Of the 64 examined endometria, 84% showed signs of estrogen stimulation, while atypical adenomatous hyperplasia was seen in 1.6%, and adenocarcinoma in 3.1%. Histologically, the diffuse growth pattern was found in one-half of the tumors, but it had no significant influence on prognosis. There was a positive correlation between cellular atypia and a high number of mitoses and increased mortality. The clinical stage had important prognostic significance. No patient younger than 40 years died from her tumor. The overall relative survival at 10 years was 80 versus 86% in Stage I. Surgery is the primary treatment of choice. Irradiation should be added in Stage II or higher. In Stage I patients, radiotherapy did not improve the prognosis. Recurrences developed as late as 22 years following primary treatment, and occurred in 21% of the patients. The prognosis in such instances is poor, and aggressive treatment is recommended. Patients with granulosa cell tumors should be followed for the rest of their lives.

Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A gynecologic oncology group study of second‐line therapy in 105 patients

One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first‐line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty‐eight percent of the patients had short‐term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).

Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study.

Ninety-six assessable patients with advanced or recurrent uterine sarcomas, who were no longer controllable with surgery and radiotherapy, and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Of 63 cases with mixed mesodermal tumors, five complete responses (CRs; 8%) and seven partial responses (PRs; 11%) were observed (95% confidence interval [CI], 10.3% to 30.9%). Of 33 patients with leiomyosarcoma, one PR (3%) was observed (95% CI, .1% to 15.8%). Adverse effects included leukopenia (23%), nausea and vomiting (73%), and mild azotemia (42%). No patients experienced life-threatening toxicity. Cisplatin has definite activity when given at the dose and schedule that we tested for patients with mixed mesodermal sarcomas who have not received prior chemotherapy, but has little activity in patients with leiomyosarcoma.

Distribution of disease at autopsy in 100 women with ovarian cancer

Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction.

Stage III ovarian tumors of low malignant potential treated with cisplatin combination therapy (A Gynecologic Oncology Group Study)

By serendipity we have had the opportunity to evaluate cis-platin-based chemotherapy in ovarian tumors of low malignant potential (LMP). Optimal (less than 1 cm residual disease) FIGO stage III ovarian carcinomas were randomly assigned to treatment with cisplatin plus cyclophosphamide with or without doxorubicin on a prospective Gynecologic Oncology Group Study. On review by the Gynecologic Oncology Group Pathology Committee, 32 of these cases were determined to represent low malignant potential tumors. Mean age of patients with these lesions was 48 years (range, 25-75 years). After initial cytoreduction, 19 patients had residual disease less than 1 cm and 13 had no residual. Twenty (62.5%) received cisplatin plus cyclophosphamide and 12 cisplatin, cyclophosphamide, and doxorubicin chemotherapy; 75% of patients received six or more courses. Second-look surgery was done in 15 cases; only six were negative. However, with a median follow-up of 31.7 months (range, 1-75), only 1 patient has died; no cancer was found at autopsy. The remaining patients are alive without clinical evidence of disease at a median of 30 months. The need for adjunctive therapy in patients with advanced LMP tumors remains speculative.

Absence of prognostic significance, peritoneal dissemination and treatment advantage in endometrial cancer patients with positive peritoneal cytology

Peritoneal cytology has been shown to be one of the prognostic factors in endometrial cancer. A series of 134 patients was seen between January 1977 and March 1985 with clinical Stage I (or treated as a clinical Stage I) endometrial adenocarcinoma at the University of Rochester Cancer Center. The majority of patients underwent extrafascial hysterectomy with the majority of washings obtained at the time of surgery. Fourteen percent (19/134) of the patients were found to have positive cytology. Eleven patients with positive cytology (11/19) were treated with local-regional pelvic treatment; the other eight patients received whole abdominal therapy. The recurrence rates were less with the local treatment than with the whole abdominal treatment groups (9.1% vs. 25%) in those patients having positive cytology. There was no statistical difference in recurrence rates between the pathologic Stage I patients with positive cytology (10%) versus those patients having negative cytology (5%), nor was there statistical difference in survival between pathologic Stage I positive or negative cytology patients. It is suggestive from this non-randomized study that positive cytology in endometrial cancer is not an independent prognostic factor and that whole abdominal irradiation did not influence outcome.

Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.

Histologic classification, lymph node metastases, and patient survival in stage IB cervical carcinoma: an analysis of 245 uniformly treated cases.

Abstract The role which histologic grading plays in the prognosis of cervical carcinoma is controversial. The basis for subdividing these lesions into small cell carcinomas and keratin- or nonkeratin-producing large cell carcinomas has usually been the assumption, though never statistically supported, that the small cell carcinomas are more aggressive. We tested this hypothesis by studying 245 FIGO Stage IB cases uniformly treated between 1970 and 1973. To evaluate prognosis, we selected two parameters: lymph node metastases and crude 2-year survival rate. Our data show that there is no statistically significant difference in either of these parameters to suggest that these malignancies behave differently in respect to keratinization or cellular size. Preliminary results suggest that patients in whom the cancer and cervical stroma have a characteristically well-demarcated interface may have improved short-term survival rates.

Second-look laparotomy in the patient with minimal residual stage III ovarian cancer (a Gynecologic Oncology Group study)

Abstract One hundred eighty-six patients with minimal residual Stage III ovarian cancer (tumor mass ⩽3 cm) were treated in a prospective randomized protocol (melphalan with or without Corynebacterium parvum ). As per protocol 84 patients were eligible and underwent a second-look laparotomy with 41 (49%) having negative findings for persistent malignancy. Factors which affected survival after second look were presence or absence of macroscopic disease, age, and grade. Depending upon these prognostic factors, survival at 4 years after second look ranged from 31 to 100%. The role of second-look laparotomy is examined relative to these results.