Patton B. Saul

Endodermal Sinus Tumor of the Vagina and Cervix

This report describes six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls younger than age 3 years simulates the presentation of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin‐D, and cyclophosphamide (VAC) for 11 months. This is the first report of such a response. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This is the first report of apparently successful therapy that allowed retention of childbearing potential. Four of the six patients have been disease‐free from 2 to 23 years. After examining the world literature, it is concluded that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vincristine, dactinomycin, and cyclophosphamide

Eighty patients with malignant nondysgerminomatous germ cell tumors of the ovary were treated with the combination of vincristine, dactinomycin, and cyclophosphamide (VAC) at The University of Texas M. D. Anderson Hospital and Tumor Institute. All patients underwent initial surgery: biopsy alone in 3 patients, unilateral salpingo‐oophorectomy in 48 patients, and bilateral salpingo‐oophorectomy with or without hysterectomy in 29 patients. Sixty‐six patients received VAC as primary postoperative therapy; 46 patients (70%) achieved a sustained remission. VAC produced sustained remission in 86% of patients with Stage I, 57% of patients with Stage II, 50% of patients with Stage III, and no patients with Stage IV disease. For patients with Stage I disease, survival rates did not differ among histologic groups, but in advanced disease, patients with immature teratoma did significantly better than the others. Four of the 20 patients who failed primary VAC therapy were salvaged with other therapies, and 8 of 14 treated with VAC after relapse or failure of other treatments were salvaged. Although VAC produces excellent results with very acceptable toxicity in patients with Stage I disease and advanced immature teratoma, survival of patients with other advanced histologic types has been disappointing. The authors are therefore treating this latter group with alternative therapy such as vinblastine, bleomycin, and cisplatin with the goal of achieving improved efficacy.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin.

Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo‐oophorectomy in ten patients, and bilateral salpingo‐oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second‐line treatment; three patients had a complete response to therapy and are surviving disease‐free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide‐containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short‐term combination regimen that has promising activity against malignant germ cell tumors of the ovary.

Carcinoma of the cervical stump

This review is a retrospective analysis of 263 patients with carcinoma of the cervical stump treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between 1963 and 1975. Symptomatology, stage distribution, and histology of carcinoma of the cervical stump showed no significant differences from cervical carcinoma of the intact uterus. Depending on the tumor stage, tumor volume, and distorted anatomy, treatment consisted of various combinations of intracavitary radium and transvaginal and external radiation. The 5-year survival was 100% in stage 0, 91% in stage I, 77% in stage II, 46% in stage III, and 37% in stage IV. The results achieved are similar to those in cervical cancer of the intact uterus. The complication rate was 30% and there were 9 (3.7%) deaths related to radiation complications.

Alveolar rhabdomyosarcoma of the female genitalia

Eight cases of alveolar rhabdomyosarcoma of the female genitalia were diagnosed from 1963 to 1983 at The University of Texas M. D. Anderson Hospital. The primary sites were vulva in two, perineum in five, and broad ligament in one patient. When possible, therapy was initiated with local tumor excision (five patients). Surgery was followed by local or regional radiation (six patients) and chemotherapy (seven patients). Of the eight patients, five died within 9 months, one died 27 months after diagnosis, and only two are 5‐year survivors. The aggressive behavior of this tumor is evidenced by autopsy findings of widespread metastases. Metastatic disease to the bone was present in four patients and to the breast in three patients. Local disease was controlled in two patients who died of distant metastases. Current therapy recommendations include excisional surgery, local radiation, and combination chemotherapy. A need for more effective chemotherapeutic programs is evident.

Urinary conduits in gynecologic oncology.

Over an 11-year period (1971 to 1981), 212 urinary conduit surgeries were performed by the Department of Gynecology at the University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston. The urinary diversions were performed as part of the pelvic exenteration operation in 154 patients, for radiation injury in 48 patients, and for palliation of disease recurrence in ten patients. Ninety-three percent had prior pelvic radiotherapy. Various segments of the gastrointestinal tract were used, including the ileum (102), sigmoid colon (99), transverse colon (four), jejunum (four), and others (three). Fifty percent of abnormal preoperative intravenous pyelograms reverted to normal after urinary diversion. Revision of the stoma was required in 6%. Other complications included infection (18%), renal loss (17%), and urinary leaks and fistulae (3%). The overall perioperative mortality was 7%, decreasing from 11% in the first five years to 3% during the last six years. Ureteral stents were routinely used. When selecting a segment of bowel for a urinary conduit, both tissue quality and mobility are important. Mortality and morbidity of urinary conduit surgery continues to decrease with experience.

Cisplatin, vinblastine, and bleomycin combination therapy in resistant gestational trophoblastic disease

Eleven patients were treated with cisplatin, vinblastine, and bleomycin (PVB) combination chemotherapy after failure of conventional triple‐agent therapy with methotrexate, dactinomycin, and cyclophosphamide for gestational trophoblastic disease. Often evaluable patients, five (50%) achieved negative titers. Sustained remission was achieved in only two patients (20%). Major hematologic toxicities and two deaths due to sepsis occurred in this group of patients. Although this combination does exhibit activity, its clinical use in the treatment of refractory trophoblastic disease is limited.

Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: Tolerance and toxicity

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

A phase II trial of 4-demethoxydaunorubicin in refractory epithelial ovarian cancer.

Sixteen evaluable patients with refractory epithelial ovarian cancer were treated with oral 4-demethoxydaunorubicin. The drug was given in divided doses over 5 days and dosage was repeated every 3 weeks. There were no objective remissions. Three patients had stabilized disease of 5 to 7 months duration. Although well tolerated, this anthracycline has modest effectiveness against previously treated ovarian cancer.

Preoperative radiotherapy for early endometrial carcinoma

A retrospective study was undertaken to compare the use of one versus two preoperative radium systems for early endometrial carcinoma. The charts of 73 patients treated between 1977 and 1980 were reviewed. No difference was noted between the two groups when compared for stage, grade, depth of myometrial invasion, and histologic type of tumor. One of thirty-eight (2.6%) patients in the one-radium group developed an isolated central recurrence; there were no central recurrences in the two-radium group. Total duration of therapy and total hospitalization for the one-radium versus the two-radium group were 17.6 and 15.3 days versus 77.0 and 17.3 days, respectively. Follow-up ranged from 48 to 84 months. Corrected survival figures are comparable to 94.6% for the one-radium group versus 100% for the two-radium group. These data suggest comparable effectiveness and morbidity between the two treatment regimens, with the single-radium application more efficient and cost effective.