Radiotherapy For Endometrial Carcinoma Research Articles

Postoperative radiotherapy for Stage 1 endometrial carcinoma: Long-term outcome of the randomized PORTEC trial with central pathology review

In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse.

48 oral Prognostic factors on adjuvant radiotherapy of endometrial carcinoma: experience with external beam radiotherapy and high-dose rate brachytherapy

48 oral Prognostic factors on adjuvant radiotherapy of endometrial carcinoma: experience with external beam radiotherapy and high-dose rate brachytherapy

The morbidity of treatment for patients with stage I endometrial cancer: results from a randomized trial

Purpose: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial. Methods and Materials: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French‐Italian glossary. Results: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1‐ 4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3‐ 4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1‐2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p 0.001). The 4-field box technique was associated with a lower risk of late complications (p 0.06). Conclusion: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity. © 2001 Elsevier Science Inc.

The morbidity of treatment for patients with stage I endometrial cancer: results from a randomized trial

Purpose: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial. Methods and Materials: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French–Italian glossary. Results: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1–4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3–4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1–2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p = 0.001). The 4-field box technique was associated with a lower risk of late complications (p = 0.06). Conclusion: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.

123 Post-operative radiotherapy for endometrial carcinoma with pathologic risk factors: Patterns of failure

123 Post-operative radiotherapy for endometrial carcinoma with pathologic risk factors: Patterns of failure

430 - Factors determining late complications following postoperative radiotherapy in endometrial carcinoma

430 - Factors determining late complications following postoperative radiotherapy in endometrial carcinoma

Pelvic fractures following irradiation for endometrial carcinoma

Purpose : To investigate the incidence and etiologic factors of pelvic fractures following radiation therapy for endometrial carcinoma. Methods and Materials : Tumor registry and radiation oncology records of patients treated for endometrial carcinoma at The Toledo Hospital between April 1989, and December 1992, were reviewed. Patients identified as having pelvic fractures without the presence of metastatic disease underwent total body mineral density measurement with dual x-ray densitometry. Results : Two of 75 patients (2.7%) were found to have pelvic fractures an average of 29 months from the completion of postoperative irradiation. One patient, who received preoperative irradiation, was also identified as having developed a fracture of the pelvis and was included in the analysis. All patients were treated prone with 10–15 MV photons in four fields daily. All three fracture patients received 45 Gy external beam radiation therapy. The two postoperative patients each received a single vaginal brachytherapy application delivering 20 Gy to 0.5 cm deep to the vaginal mucosa with a vaginal cylinder containing 30 mgRaeq 137Cs. The preoperative patient received a single brachytherapy application with tandem and colpostats delivering 20 Gy to point A. Only one of the three fracture patients had the entire pubis included in the field of external beam treatment. One patient was taking nonsteroidal anti-inflammatory medication, one patient thyroid hormone replacement, and one patient was taking both types of medication. Conclusion : The etiology of pelvic fractures after irradation is multifactorial. A complete medication history should be obtained, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the iniation of the radiation treatment.

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 11 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 11 endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

Exclusive radiation therapy in endometrial carcinoma

Purpose : From 1967 to 1986, 250 patients with endometrial carcinoma were treated with exclusive radiation therapy: 178 with a minimal follow-up of 5 years and 146 with a minimal follow-up of 10 years. The mean age was 68 years, ranging from 53 to 82 years, and the median follow-up duration was 8.5 years (minimum of 5 years and maximum of 23 years). Methods and Materials : All the patients received an external beam radiation treatment (45 Gy in 4.5 to 5 weeks to the whole pelvis) followed by a utero-vaginal brachytherapy. Results : At 5 years, the overall survival rate was 58.4% and the disease-free survival rate 55%. At 10 years the overall survival rate was 46.5% and the disease-free survival rate was 45.2%. Without considering deaths from intercurrent disease, the overall survival rate was 76.5% and the disease-free survival rate was 65.8% after 5 years, and 68% and 66%, respectively, after 10 years. The causes of failure were: isolated metastasis: 7.3%, local failure: 24.1% (4.5% with and 19.6% without concomittent distant metastasis). The rates of local control and of survival are related to the tumor stage and the tumor grade. Conclusion : The results are discussed according to the literature data and show the ability of exclusive radiation treatment to achieve acceptable results and to be a curative alternative for treating endometrial cancer providing that a correct external beam radiation therapy and a suitable brachytherapy are fulfilled.

Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: A Gynecologic Oncology Group study

The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160–180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m 2 starting dose) to a maximum cumulative dose of 500 mg/m 2. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DOX) treatment arm, and 89 patients entered the no-DOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63–70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, progression, and survival of the endometrial cancer study population. The combination of surgical staging and postoperative radiation as used in this study appears to increase the risk of bowel complications.

Postirradiation Malignant Fibrous Histiocytoma Expressing Cytokeratin

A malignant fibrous histiocytoma of the sacrum complicating the course of radiation therapy for endometrial carcinoma is presented. Although the tumor fulfilled the clinical, radiologic, and histologic criteria for a postirradiation malignant fibrous histiocytoma of bone, it also expressed cytokeratin. That this immunoreactivity reflected keratin synthesis by the tumor and not an unusual pattern of cross-reactivity with another intermediate filament such as vimentin is strongly suggested by the reproducibility of the immunoreactivity utilizing both polyclonal and monoclonal antibodies and extinction of the immunoreactivity following absorption of the primary antiserum with keratin proteins. This is the first reported instance of keratin expression by a malignant fibrous histiocytoma; it indicates that sarcomas apart from synovial sarcoma and epithelioid sarcoma may sometimes express this protein.

Urologic complications following radiotherapy of cancers of the corpus uteri

Patients with endometrial carcinomas who have undergone only radiation therapy represent a negative selection, because of the many concomitant diseases. In the author's group of 134 cases such patients were on average 7 years older than those who had undergone surgery. Even with computer-calculated opposing-field therapy with intracavity packing, radiation damage to the urinary tract must be expected. Of the 134 patients, 75 (55.9%) had pathologic urological findings following radiation therapy. The most commonly affected organ was the bladder (55.2%), followed by the kidneys (21.6%) and the ureter (7.5%). Radiation damage to the urethra could not be verified. The urological complications were hardly affected by the stage of the tumor, but considerably so by the time interval: the rate of urological complications was 68.9% higher after 5 years than after 1 year. Therefore, accurate statements concerning urological complications following primary radiation therapy for endometrial carcinoma cannot be made until 5 years have elapsed.

The significance of residual disease after radiotherapy in endometrial carcinoma: Clinicopathologic correlation

The extent and location of residual disease after radiotherapy in 91 patients with early invasive endometrial carcinoma was related to tumor grade, clinical stage, and outcome. In 20% the grade (according to the International Federation of Gynecology and Obstetrics) differed in curettage and hysterectomy specimens. In at least 12% the clinical stage was unreliable. Death from endometrial carcinoma was significantly more frequent in patients with residual disease after radiotherapy than in those without residual disease. The poorest prognostic features were blood vessel invasion in the myometrium, irrespective of depth of invasion, and residual disease outside the uterus. Treatment of endometrial carcinoma should be based on accurate knowledge of prognostic features determined by initial surgery.

Use of ultrasonography in planning intracavitary radiotherapy of endometrial carcinoma.

A diagnostic ultrasound examination is a simple and reliable method of obtaining anatomical information for intracavitary irradiation of endometrial carcinoma of the uterus. Scanning before treatment to determine uterine size and shape assists in choosing the most appropriate applicator. Scanning after insertion of an afterloading applicator facilitates calculation of radiation doses at critical points within and on the surface of the uterus. Poor applicator position can also be detected. Diagnostic ultrasound examinations should be adopted as a routine procedure in establishing intracavitary irradiation programs for adenocarcinoma of the uterine fundus.

Use of ultrasonography in planning intracavitary radiotherapy of endometrial carcinoma

Use of ultrasonography in planning intracavitary radiotherapy of endometrial carcinoma

Preoperative radiation therapy in endometrial carcinoma: preliminary report of a clinical trial

A total of 91 patients with stage I endometrial adenocarcinoma who were referred for radiation prior to hysterectomy were randomly allocated to recieve either intracavitary or external bean irradiation. Total abdominal hysterectomy was done 4-8 weeks later. The 53 patients who received intracavitary irradiation had an actuarial 5 year disease-free survival rate of 75%; the survival rate of the 38 patients in the external beam group was 48%. Nine patients in the external beam group had recurrence or metastases compared to two in the intracavitary group. These recurrences were predominantly pelvic. Complications were also more frequent in the external beam group. These results demonstrate that intracavitary radiation is superior to external beam radiation using the regiments described.

Histopathologic analysis of preoperative radiation therapy in endometrial carcinoma

One hundred and sixteen patients with Stage I endometrial carcinoma were treated by hysterectomy with or without preoperative radiation therapy. Survival was slightly but not significantly increased in the group who received preoperative irradiation. The survival rates were identical when examination of the hysterectomy specimen showed no residual tumor or tumor limited to the endometrium after radiation, but survival was significantly poorer when myometrial extension was present. The incidence of complete tumor sterilization was considerably higher in uteri removed more than 5 weeks following the completion of radiation therapy. When residual tumor was present after radiation, its histologic characteristics were seldom altered from those observed in material obtained before treatment, and bizarre radiation changes were seen almost exclusively in benign endometrial glands. Our data indicate that carcinomas limited to the endometrium are frequently sterilized by preoperative radium but that survival is not changed appreciably in these cases. Tumors with myometrial extension, which have a poorer prognosis, appear to be considerably less frequently sterilized by the techniques employed in this series. Implications for therapy based on these histologic data are presented.

Use of pelvic pneumography in planning radiotherapy of endometrial carcinoma.

Knowledge of the size, shape, and location of the uterus as obtained by pelvic pneumography can be used in planning preoperative intracavitary irradiation in cases of endometrial carcinoma. Radioactive sources maybe distributed and treatment administered so that maximum tolerance of surrounding normal tissues is not exceeded in the case of a small uterus, nor is the large uterus undertreated. The dose to the uterus is expressed as an absorbed dose in rads. The author describes the technique of the examination and the development of the therapy program.