Recent studies on chemotherapy are here and below

Some of the studies (conflicting data) concerning the role radiation are noted below and the studies on use of chemotherapy are noted here.

Cancer 1990 Jul 1;66(1):35-39

Treatment of uterine sarcomas.

Echt G, USC School of Medicine

During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.
 

Am J Obstet Gynecol 1987 Mar;156(3):660-662

Adjuvant therapy for stage I uterine sarcoma.

Rose PG, Boutselis JG, Sachs L

A retrospective evaluation of adjuvant therapy in 64 patients with Stage I sarcoma was undertaken. A combination of operation and adjuvant radiation was compared with operation alone. A decreased recurrence of both pelvic and distant tumor was noted for endometrial sarcoma but not for leiomyosarcoma treated with adjuvant radiation. A Cox regression analysis showed a trend for improved survival, but the results were not statistically significant. Survival after vaginal cuff recurrence and treatment with radiation therapy (two patients) or combined radiation and chemotherapy (one patient) is reported. Seven patients received adjuvant chemotherapy with Adriamycin-based regimens. Chemotherapy alone did not statistically decrease recurrence in this small sample.
 

Radiology 1975 Jan;114(1):181-188

Uterine sarcoma.

Belgrad R, Elbadawi N, Rubin P

Thirty-four cases of uterine sarcoma were studied with regard to their pathologic characteristics and response to treatment. Pathologic features did not always correlate with subsequent course. Combined therapy seems to enhance two-year survival in endometrial stromal sarcoma (ESS), although some patients may have low-grade tumors and hence represent a more favorable group. Adjuvant irradiation may improve local control rates in some mixed mesodermal sarcomas (MMS), but does not add appreciably to survival. It is of doubtful benefit in the leiomyosarcoma (LMS) group. When irradiation is employed, preoperative therapy is preferred except in the highly malignant mixed mesodermal sarcomas where prompt surgery seems indicated first. Supplemental brachytherapy may also be employed.

Obstet Gynecol 1975 Jan;45(1):84-88

The value of radiation therapy in uterine sarcoma.

Gilbert HA, Kagan AR, Lagasse L, Jacobs MR, Tawa K

Fifty-eight cases of leiomyosarcoma of the uterus and 47 endometrial sarcomas of the uterus are reviewed based on the pertinent information related to recurrence patterns. The following conclusions are made: 1) Cases of endometrial sarcoma should receive preoperative pelvic irradiation, or postoperative pelvic irradiation if a diagnosis is not made until the postoperative period. This plan will probably be of most benefit, if at all, in stage 1 disease. 2) A case for pelvic irradiation as an adjuvant to surgery in leiomyosarcoma cannot be made from a review of this material, either from a viewpoint of recurrence patterns or radio-responsiveness.
 

Int J Radiat Oncol Biol Phys 1986 Dec;12(12):2127-2130

Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma.

Hornback NB, Omura G, Major FJ

From November 1973 through July 1982, 225 women with Stage I or II uterine sarcoma were entered on a protocol which evaluated the use of doxorubicin in the adjuvant setting. Of these, 157 patients had a minimum follow-up of 2 years. Following complete surgical removal of all known clinical disease, consenting patients were randomized to receive either 60 mg/m2 of doxorubicin every 3 weeks for eight courses or no further therapy. The use of radiation therapy in this protocol was optional, and a review of protocol cases was undertaken to determine progression-free interval, survival rates, and site of first recurrence in the radiation therapy and no radiation therapy groups. In patients with Stage I or II leiomyosarcoma of the uterus, there was no difference in the progression-free interval, absolute two-year survival rate, or site of first recurrence in the two groups. There was no difference in the progression-free interval or absolute survival rates for cases with Stage I and II uterine mixed mesodermal sarcomas in the two treatment groups. However, those who received radiation therapy to the pelvis experienced a statistically significant reduction of recurrences within the radiation treatment field.
 

Radiother Oncol 1990 Feb;17(2):123-132

Mixed mullerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases.

Larson B, Silfversward C, Nilsson B, Pettersson F

Department of Obstetrics and Gynaecology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.

One hundred and forty-seven women with uterine mixed Mullerian tumours (UMMT) treated at Radiumhemmet from 1936 through 1981 were reviewed. The prognostic value of clinical and histopathologic data was analysed with bivariate and multivariate techniques. Stage, age and abdominal pain were found to be significant predictors of survival. Surgery and combined radiotherapy (intracavitary + external irradiation) gave in stage I, a lower local failure rate and better overall survival than surgery in combination with either intracavitary or external irradiation.

Eur J Obstet Gynecol Reprod Biol 1990 May;35(2-3):239-249

Endometrial stromal sarcoma of the uterus. A clinical and histopathological study. The Radiumhemmet series 1936-1981.

Larson

Twenty-eight cases of endometrial stromal sarcoma treated from 1936 to 1981 at Radiumhemmet were reviewed. Histopathologically, 16 were classified as high-grade stromal sarcomas and 12 were of a low grade. A significant relation between mitotic count and relative survival within 10 years of the diagnosis was found (p less than 0.05) showing a more favorable outcome for patients with low counts compared with patients with higher counts. Primary treatment included surgery and radiotherapy in 21 cases. Two advanced cases were only irradiated and five cases were treated with surgery alone. Adjuvant radiotherapy seems to be of benefit in high-grade tumors, demonstrated in a 5-year survival rate of 73%, which exceeds most reported results. Five out of seven women dying of low-grade tumors were diagnosed in an advanced stage.
 

Obstet Gynecol 1986 Mar;67(3):417-424

Sarcomas of the uterus: a clinicopathologic study of 119 patients.

Kahanpaa

This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed mullerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed mullerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.
 

J Clin Oncol 1985 Sep;3(9):1240-1245

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

Omura GA, Blessing JA, Major F, Lifshitz S, Ehrlich CE, Mangan C, Beecham J, Park R, Silverberg S

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.

Gynecol Oncol 1989 Sep;34(3):323-327

Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors.

Peters WA 3d, Rivkin SE, Smith MR, Tesh DE

Puget Sound Oncology Consortium, Seattle, Washington 98104.

Twenty-eight patients with a uterine stromal sarcoma or mixed mesodermal tumor were treated with cisplatin 100 mg/m2 and Adriamycin 45-60 mg/m2, given with intravenous hydration every 3 to 4 weeks. Group I consists of 11 patients with measurable disease following initial surgery or with a recurrence. Eight of the eleven evaluable patients with measurable disease had a response (73%), and three of these patients have had a negative second-look procedure, and two are alive and disease free more than 24 months after initiation of treatment. Group II consists of 17 patients treated with adjuvant chemotherapy after primary surgery. The patients were selected for adjuvant therapy based on previous established poor prognostic features. Of the 17 patients in group II, 14 had invasion of the outer one-third of the myometrium and the other three had invasion to the middle one-third. Seven had documented positive pelvic and/or periaortic lymph nodes and five had positive peritoneal washings. With a median follow-up of 34 months, there have been only four recurrences in group II. Two of the recurrences occurred in patients who discontinued therapy after only two cycles of chemotherapy. There is a projected 5-year survival of 75% in these high-risk patients. Of the seven patients with documented nodal involvement, one patient died with a recurrence at 23 months, one patient died from a perforated diverticulum, and the other five are alive and disease free with a median follow-up of 36 months (34-90 months). Two patients with multiple positive nodes are disease free at more than 5 years. Combination chemotherapy with cisplatin and Adriamycin has a high response rate with advanced measurable disease and improves survival in high-risk patients who receive it as adjuvant therapy.