Brachytherapy for early endometrial carcinoma: a comparative study with long-term follow-up.

The current study was undertaken to evaluate the effect of preoperative uterine or postoperative vaginal brachytherapy compared to no adjuvant therapy on the disease-free interval, sites of recurrence, and survival in favorable stage IB endometrial carcinoma. One hundred and forty-six patients with FIGO grade 1 and 2 endometrial carcinoma and 1-33% myometrial invasion treated between 1974 and 1992 were retrospectively studied. The use of brachytherapy varied among the treating physicians during the study period. A Kaplan-Meier survival analysis was used to estimate disease-free survival and differences between treatment groups were evaluated with the Mantel-Cox statistic. Recurrent disease occurred in 7 patients (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences. Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors (P = 0.04). Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with brachytherapy vs. 10.3% of those not treated (P = 0.68). Brachytherapy did not affect the disease-free or overall survival. No serious complications directly related to therapy occurred. Vaginal recurrences occur even in early endometrial carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger study would be required to see a recurrence or survival difference.

Primary radiation therapy for endometrial carcinoma: a case controlled study.

PURPOSE: Primary radiation therapy is generally considered inferior to a surgical approach for patients with endometrial carcinoma and is reserved for patients with a high operative risk. These patients are usually elderly, have multiple medical problems and frequently die of intercurrent disease. To evaluate the efficacy of primary radiation therapy a case controlled analysis comparing corrected survival of patients treated with primary radiation to patients treated with surgical therapy with or without radiation therapy was performed. METHODS AND MATERIALS: Sixty-four patients treated with primary radiation therapy were retrospectively studied. A Kaplan-Meier product limit survival analysis was used to estimate survival among patients treated with primary radiation therapy. A case control study matched by clinical stage, tumor grade, and time of diagnosis was performed. The Mantel-Cox statistic was used to evaluated the equality of the survival curves. RESULTS: Primary radiation therapy was used to treat 9.0% of the patients with endometrial carcinoma during the study period. Cardiovascular disease, diabetes, age greater than 80 and morbid obesity were the most common indications. Ninety percent of patients had either Stage I or II disease. Forty-eight of the 64 patients (75%) completed treatment which included both teletherapy and brachytherapy. Ten patients received brachytherapy only. Twelve complications, both acute and chronic, occurred in eleven patients (17%). Intercurrent disease accounted for 13 of the 36 (36%) of the deaths. Clinical stage of disease and histologic grade of the tumor were significant predictors of survival, p = 0.0001 and p = 0.013, respectively. The case controlled study of Stage I and II patients treated by primary radiation therapy matched to surgically treated controls showed no statistical difference in survival. Dilatation and curettage after the completion of radiation therapy was predictive of local control, p = 0.003. CONCLUSION: Although surgery followed by tailored radiation therapy has become widely accepted therapy for Stage I and II endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

Squamous cell carcinoma arising in a mature cystic teratoma with metastasis to the paraaortic nodes.

Accurate surgical staging is critical to the management of early ovarian cancers. A patient with squamous cell carcinoma arising from a mature cystic teratoma was found to have paraaortic nodal metastasis as her only evidence of extraovarian disease. Extended field radiation therapy to the pelvis and paraaortic nodes with concomitant cisplatin and adjuvant chemotherapy failed to control her disease. Inadequate surgical staging may explain the recurrences in apparent stage I disease.

Accuracy of frozen-section diagnosis at surgery in clinical stage I and II endometrial carcinoma.

OBJECTIVES: The purpose of our study was to determine if frozen section accurately identifies certain poor prognostic pathologic factors in endometrial carcinoma that are known to be associated with pelvic and paraaortic nodal metastasis, including deep myometrial invasion, poorly differentiated tumor, cervical invasion, adnexal involvement, and poor histologic type. STUDY DESIGN: The frozen-section pathologic results of 199 patients with clinical stage I and II endometrial cancer were retrospectively compared with permanent-section pathologic findings. RESULTS: The depth of myometrial invasion (superficial third vs deep two thirds) was accurately determined by frozen-section diagnosis at surgery in 181 of 199 cases (91.0%). The sensitivity of frozen-section diagnosis for deep myometrial invasion was 82.7%, and the specificity was 89.1%. The following tumor characteristics were accurately determined on frozen section at surgery: poorly differentiated tumor (95.0%), cervical invasion (94.0%), adnexal involvement (98.5%), and histologic type (94.0%). Frozen section underestimated deep myometrial invasion in 17.3% of patients with this characteristic and poorly differentiated tumor in 26.3% when compared with permanent-section diagnosis. In patients with unfavorable histologic types, papillary serous and adenosquamous carcinomas were the most commonly misdiagnosed histologic types by frozen section at surgery (70.6%). However, when the preoperative curettage pathologic findings were included, these inaccuracies in tumor grade and histologic type dropped to 15.8% and 35.3%, respectively. Only 13 of 199 patients (6.5%) were not correctly identified by frozen section at surgery as having poor prognostic pathologic features. CONCLUSION: Frozen section diagnosis at surgery is an important procedure that enables the surgeon to identify patients at high risk for pelvic and paraaortic nodal metastasis.

Radiation therapy for surgically proven para-aortic node metastasis in endometrial carcinoma.

The impact of para-aortic field radiation therapy upon survival was studied among 26 patients with para-aortic nodal metastases from carcinoma of the endometrium. Seventeen of these 26 patients received postoperative radiation therapy to the para-aortic field as a part of their primary therapy. Sixteen of the 17 also received adjuvant hormonal therapy. Nine of 17 patients (53%) are alive without evidence of disease (18-55 months) with a median survival time of 27 months. Of the remaining eight patients, six (35%) died of endometrial cancer at 6-38 months, with a median survival time of 14.5 months. Five of these patients had distant disease. Two of the 17 patients (12%) died of intestinal obstruction felt to be secondary to radiation enteritis, one of whom was disease free. No difference in survival was detected in patients treated with radiation therapy with microscopic versus macroscopic nodal involvement. Of the nine patients who did not receive para-aortic radiation, eight were treated with hormonal therapy (n = 6) or chemotherapy (n = 2). Seven patients died of disease from 5-28 months, with a median survival time of 13 months. One patient is alive at 12 months. Survival in the 17 patients treated with para-aortic radiation was better than the eight patients not treated with para-aortic radiation (p = 0.004). This survival difference remained significant for patients with microscopic but not macroscopic nodal disease. Para-aortic field radiation appears to improve survival, but has a significant complication rate, and should be reserved for patients with histologic evidence of para-aortic metastases.

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer.

Sixty-one patients with epithelial ovarian cancer were treated with intensive high-dose, short-course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second-look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole-abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/microliter and platelet nadir of 90/microliters. Forty-five patients (74%) had a complete clinical response. Results of twenty-two of 36 second-look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole-abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High-dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low-dose regimens. Although high-dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second-line therapy.

Adenoid cystic carcinoma of the vulva: a radiosensitive tumor.

A patient with adenoid cystic carcinoma of the vulva treated primarily with surgery developed multiple local and distant recurrences in which radiotherapy repeatedly achieved complete local control. The patient survived 11.5 years from original diagnosis and 9.5 years from primary recurrence before dying of pulmonary metastases. Adenoid cystic carcinoma of the vulva is a highly radiosensitive tumor. Adjuvant radiotherapy should be considered as a part of the primary therapy, to improve local control, on the basis of the much larger experience with adjuvant radiotherapy with this tumor in the head and neck. Also on the basis of head and neck tumors, it is unlikely that radiotherapy will affect survival.

Primary adenocarcinoma of the breast arising in the vulva.

Primary adenocarcinoma of ectopic breast tissue in the vulva has been reported in only four instances. A fifth case, in which estrogen and progesterone receptors were present, is described. Estrogen and progesterone receptor studies may be helpful in identifying adenocarcinoma of uncertain origin.

Treatment of advanced ovarian cancer with sequential combination chemotherapy.

Fifty previously untreated patients with advanced or recurrent ovarian cancer (FIGO Stages III and IV) were treated with alternating combination chemotherapy. This consisted of high-dose doxorubicin (70 mg/m2) and cisplatin (100 mg/m2) alternated with CHF (cyclophosphamide, hexamethylmelamine, and 5-fluorouracil). Toxicity (myelosuppression, nephropathy, and neuropathy) was infrequent and mild. Clinical response rates were high (94% response, 62% complete clinical response), but the majority of patients had residual intraabdominal disease at second-look surgery (75%). Thirteen patients (26%) are alive after 4 years of observation (minimum follow-up). Survival was adversely influenced in patients who were older than 70, had Stage IV disease, residual tumor bulk greater than 2 cm, and who failed to achieve complete clinical remission. The median duration of survival (28 months) and percentage of long-term survivors appear similar to that in other platinum-based chemotherapy studies. Although the role of alternating combination chemotherapy in epithelial ovarian cancer remains undefined, it is likely that an alternate approach will be necessary to markedly improve survival rates for patients with this disease.

Preoperative irradiation of primarily unresectable colorectal carcinoma.

A series of 44 patients with colorectal carcinomas considered unresectable on presentation received preoperative irradiation to a dose of 4500--5000 rad (175--200 rad/day). After a waiting period averaging 6.5 weeks, 38 patients underwent exploration. Complete resection was possible in 27 patients. Of these, 22 patients remained disease-free with a median follow-up of 27 months. While longer follow-up periods are needed, the results indicate that the large percentage of unresectable and therefore surgically incurable colorectal carcinomas can be made resectable by preoperative irradiation, and a significant number of these may have been cured.

Myometrial invasion and hysterography in endometrial carcinoma.

One hundred and seventy-nine patients with endometrial carcinoma underwent hysterography as part of their pretreatment evaluation. One hundred and twenty-six women received preoperative irradiation followed by hysterectomy; 30 had surgery alone; while 23 received radical radiotherapy. We have classified hysterograms by the degree of tumor invasion suggested radiographically and have compared these, in the operated cases, with postoperative pathologic examination. Characteristically, lesions confined to the endometrium, or with superficial myometrial penetration, demonstrate either no radiologic abnormality or a small, shallow defect by hysterogram. In those patients with deep myometrial invasion of cancer, hysterograms usually demonstrate a large defect in the endometrial cavity. We believe that hysterography helps assure optimum treatment of each individualized case by helping to determine the volume of tumor and extension into the myometirum.

The role of interstitial therapy in present day radiotherapy.

The role of interstitial therapy in the treatment of malignant tumors is discussed. With interstitial therapy, the tumor is accurately localized under general anesthesia, irradiation is limited to the tumor-bearing volume of tissues with minimal irradiation of normal structures, and treatment time is shorter than with external beam therapy. Disadvantages include its rather limited clinical application, more complicated dosimetry, the higher level of technical skill required in the surgical procedure, and radiation exposure of operator and personnel. Interstitial therapy is indicated for relatively small well differentiated primary tumors and in cases where the primary and lymph node metastases are in close proximity. A combination of interstitial and external beam therapy is recommended for advanced tumors and in cases of unsatisfactory implants. Seven illustrative cases are presented. It is recommended that improved afterloading techniques and surgical and nonsurgical procedures (e.g.,suspension laryngoscope) be developed so that this type of therapy can be extended to all cases requiring high doses and a small volume of radiation.