Clinical stage I endometrial cancer: results of adjuvant irradiation and patterns of failure

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively from January 1960 through December 1986 with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Most patients received a preoperative intracavitary insertion (2500-4000 mgh to the uterus with Heyman capsules and tandem and 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 6 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when deep myometrial invasion was present. Occasionally patients were treated with preoperative external beam irradiation (2000 cGy whole pelvis) and intracavitary insertion. The 5-year overall survival for all patients was 84.0% compared to an expected survival of 88.8%. The 5-year progression-free survivals were 92% for FIGO clinical Stage IA and 86% for stage IB (p = 0.12). The dose to the uterine fundus from the preoperative intracavitary insertion was found to have a significant correlation with progression-free survival in patients with grade 3 tumors. Those receiving less than 2500 mgh to the uterine cavity had a 48.9% 5-year progression-free survival compared to 62.7% for 2500-3500 mgh and 87.4% for those receiving greater than 3500 mgh. Analysis of sites of failure showed that less than 1% (7/858) failed in the pelvis alone, 3% (30/858) in the pelvis combined with distant sites, and 7% (60/858) developed distant metastasis only. The lateral pelvic sidewall was the most common site of failure within the pelvis (20/37) and intraperitoneal failures (28/90) and lung (21/90) were the most common sites of distant metastasis. The overall severe (grades 2, 3, and 4) complication rate was 2.7% (23/858).     

Clinical stage I endometrial cancer: prognostic factors for local control and distant metastasis and implications of the new FIGO surgical staging system.

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) from January 1960 through December 1986. Most patients received a preoperative intracavitary insertion (3500-4000 mgh to the uterus and a 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 1-2 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when factors such as deep myometrial invasion were present. Occasionally patients were treated with a preoperative intracavitary insertion and preoperative external beam irradiation (2000 cGy whole pelvis). The 5-year progression-free survivals by FIGO (1988) surgical stage were 93% for IA, 90% for IB, and 91% for Stage IC. An analysis of multiple variables was performed to ascertain their prognostic significance. Factors that significantly affected the 5-year progression-free survivals by univariate analysis were grade (grade 1 = 95%, grade 2 = 88%, grade 3 = 73%; p less than 0.0001), histology (adenoacanthoma = 96%, clear cell = 89%, adenocarcinoma = 89%, papillary = 81%, adenosquamous = 80%; p = 0.04), lower uterine segment involvement (uninvolved = 89%, involved = 73%; p = 0.006), depth of myometrial invasion (no residual tumor = 91%, limited to the endometrium = 96%, less than 1/3 myometrial penetration = 92%, 1/3 - 2/3 = 100%, greater than 2/3 = 50%; p = 0.02), peritoneal cytology (negative = 92%, positive = 56%, p less than 0.0001), uterine serosal involvement (uninvolved = 89%, involved = 55%; p less than 0.0001), vascular space invasion (absent = 89%, present = 75%; p = 0.001), and the presence of extrauterine disease (absent = 90%, present = 64%; p less than 0.0001). A multivariate analysis of these prognostic variables showed that histological grade (p = 0.001), peritoneal cytology (p = 0.004), and uterine serosal involvement were prognostic for local failure and that peritoneal cytology (p less than 0.001), grade (p = 0.001), age (p = 0.002), and extrauterine disease (p = 0.02) were prognostic for the development of distant metastasis.     

Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ

The objective of this study was to define the role of radiotherapy alone for medically inoperable patients with Carcinoma in Situ (CIS) and Stage IA carcinoma of the uterine cervix. At the Mallinckrodt Institute of Radiology, Radiation Oncology Center from January 1959 through December 1986 21 patients with CIS and 34 with Stage IA were treated. All patients had histologically proven disease. The average age was 56 years for CIS and 51 years for Stage IA patients. Therapy for patients with CIS consisted of a single intracavitary insertion with a uterine tandem and colpostats. The average radiation doses were 4612 cGy to point A, 9541 cGy to the surface of the cervix, and 5123 milligram-hours (mgh). Radiotherapy for Stage IA tumors was delivered with intracavitary irradiation alone in 13 (average doses were 5571 cGy to point A, 10,430 cGy vaginal surface dose, and 6488 mgh). The other 21 patients were treated with external beam and intracavitary irradiation. The average whole pelvis dose was 1443 cGy with an additional 2354 cGy boost to the parametria with a midline stepwedge shield. The average intracavitary doses were 5200 cGy to point A, 10234 cGy to the vaginal surface, and 6293 mgh. None of the patients with CIS developed recurrent disease and none had severe sequelae of therapy. Only one patient with Stage IA developed recurrent disease in the pelvis. None developed metastatic disease. The severe complication rate was 5.9% (2/34) for Stage IA and only occurred in those receiving intracavitary irradiation and external beam irradiation. We conclude that irradiation consisting of intracavitary implants alone is excellent treatment for patients with medically inoperable Stage IA and CIS of the cervix.     

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prognostic significance of interval from preoperative irradiation to hysterectomy for endometrial carcinoma

From 1965 through 1980, 193 patients with histologically proven endometrial carcinoma, FIGO-AJC Stage I-III, received preoperative radiation therapy. One hundred forty-two patients had Stage I (G1:41, G2:68, G3:33), 47 Stage II, and 4 Stage III endometrial carcinoma. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). They were followed from 3 to 18 years (median, 6.2 years) after the completion of the treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 85%. The interval between the completion of radiation therapy and TAH-BSO ranged from 3 days to 123 days (median, 40 days). Five-year and 10-year survivals were 95% among 65 patients who did not have residual cancer in the hysterectomy specimen compared to 75% and 70%, respectively, among 128 patients who had positive hysterectomy specimens (P less than 0.01). The presence or absence of residual carcinoma in the surgical specimen after preoperative irradiation was the only important prognostic variable. The most significant factors associated with residual cancer cells were the interval from the completion of radiation therapy to TAH-BSO (P less than 0.001) and the method of preoperative irradiation in patients with Stage I Grade 3 and Stage II external pelvic irradiation was less frequently associated with residual cancer than intracavitary applications (P = 0.043). With one exception, all patients who failed had residual cancer in the hysterectomy specimen. The depth of myometrial invasion of residual tumor in the hysterectomy specimen after preoperative irradiation was correlated to the frequency of failures (P = less than 0.05). Failures were distributed equally among the pelvis, para-aortic nodes, and distant sites. Complications of treatment were infrequent (7%) and were mild; no fatal complications were seen. The data suggest an optimal interval for hysterectomy is 29 to 42 days after completion of radiation therapy in unfavorable carcinomas of the endometrium. These patients also benefit from external pelvic irradiation with or without intracavitary applications as this therapy provides the highest probability there will be no residual cancer cells in the surgical specimen.     

Preoperative whole pelvis versus true pelvis irradiation and/or cystectomy for bladder cancer

Between 1949 and 1974, 449 patients with bladder cancer were treated by radical cystectomy either alone (137 patients or following three preoperative radiation schemes (312 patients). True pelvis irradiation was delivered either 4000 cGy (rad) over 4 weeks in 119 patients, or 2000 cGy over 1 week in 86 patients; radical cystectomy was performed after periods averaging 6 weeks.and 2 days, respectively. Whole pelvic irradiation of 2000 cGy in 5 consecutive days was given to 107 patients who underwent cystectomy within 2 days later. Five-year survival rates for low-stage TIS-T₂ tumors of low histologic grade were 60–66% in the four treatment groups. The 5-year survival for high-stage tumors of high histologic grade, mainly in T₃ patients, was 9% in the cystectomy alone patients versus 24–32% in the preoperatively irradiated patients. The 5-year survival rates for high-stage low-grade and low-stage high-grade tumors, were 30% in the cystectomy alone group and 39–51% in the preoperative irradiation groups; the more favorable survival was noted in the whole pelvic irradiation group, which included 18% 5-year survivals for T₄ patients. Pelvic recurrence was reduced from 28% after cystectomy alone to 14–16% with true pelvis irradiation and 8% with whole pelvic irradiation. The reduced incidence of local recurrence, observed mainly in high stage or high grade tumors, was associated with tumor downstaging after irradiation. Extrapelvic metastases developed in 21–35% of the four treatment groups, underlining the inadequacy of the local radiation and surgical treatment in preventing subsequent distant spread.     

局部晚期宫颈癌CT图像引导下适形调强后程推量的临床研究

目的：观察利用三维适形调强技术（Intensity modulated radiotherapy,IMRT）、采用5Gy×5f分割模式对于局部晚期宫颈癌患者盆腔外照射后残留病灶局部推量的治疗效果及并发症发生。方法：33例局部晚期宫颈癌患者在完成盆腔外照射及同期DDP化疗后,行CT模拟定位扫描,定位前及每次治疗前均进行膀胱灌注以控制膀胱的充盈程度,勾画子宫颈、宫旁及阴道侵犯区域以及2cm阴道组织、子宫体下段2/3为CTV-boost,CTV-boost加5、15mm为PTV-boost,设计并执行7野三维适形调强计划,处方剂量为5Gy/f×5f,2f/w。结果：1年总生存率、无病生存率、盆腔控制率分别为82%、76%、79%,其中15mm PTV边界组的1年盆腔控制率为90%。结论：对于不能进行腔内后装治疗的部分局部晚期宫颈癌患者,采用5Gy×5f分割模式的三维适形调强技术进行后程推量可达到根治效果,1年内未见严重直肠、膀胱并发症出现,远期疗效及并发症正在进一步观察中。     

Definitive irradiation in carcinoma of the vagina: long-term evaluation of results

A retrospective analysis of 165 patients with histologically confirmed carcinoma of the vagina is reported. Actuarial disease-free 10-year survival was: Stage 0 (16 patients)--94%, Stage I (50 patients)--75%, Stage IIA (49 patients)--55%, Stage IIB (26 patients)--43%, Stage III (16 patients)--32%, Stage IV (8 patients)--0%. All but one of the in situ lesions were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence. Most of them received interstitial or intracavitary therapy or both; the addition of external beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) 61% of the tumors were controlled with a combination of brachytherapy and external beam irradiation. Ten of 16 Stage III tumors were controlled in the pelvis. Two of the patients with Stage IV disease had no recurrence in the pelvis with relatively high doses of irradiation. The total incidence of distant metastases was 16% in Stage I, 30.6% in Stage IIA, 46.1% in Stage IIB, 62% in Stage III, and 50% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was critical in achieving successful results. The incidence of grade 2-3 complications (12%) is correlated with the stage of the tumor and type of treatment given. More effective irradiation techniques including the optimization of dose distribution by judicious combination of external irradiation and interstitial brachytherapy will be necessary to enhance loco-regional tumor control. The high incidence of distant metastases underscores the need for earlier diagnosis and effective systemic cytotoxic agents if survival is to be significantly improved in these patients.     

Whole abdominal irradiation for tumors of the uterine corpus

Between November 1981 and December 1985, 16 patients with high-risk tumors of the uterine corpus were treated with a postoperative course of whole abdominal-pelvic irradiation. Thirteen patients had carcinomas and three had sarcomas. All patients had complete pelvic surgery including extrafascial (or modified radical) hysterectomy and bilateral salpingo-oophorectomy, pelvic node sampling, evaluation of peritoneal cytology, and resection of extrauterine metastases when indicated. All patients were free of gross visible tumor after surgery. Target doses of radiation were 3000 cGy to the upper abdomen and 4500 cGy to the pelvis. Median follow-up was 24 months for survivors (range, 17 to 63 months). The disease-free survival and overall survival at 17 months was 50%. Six of the 16 (38%) patients suffered intraabdominal relapse. One patient had a significant complication (bowel perforation). The data from this pilot study suggest that whole abdominal-pelvic irradiation may be useful only in the management of some patients with few high risk features of endometrial carcinoma. Patients with extensive extra-uterine involvement and with sarcoma histology do not appear to benefit from this experimental therapy.     

Factors affecting long-term outcome of irradiation in carcinoma of the vagina

OBJECTIVE: This report evaluates prognostic and technical factors affecting outcome of patients with primary carcinoma of the vagina treated with definitive radiation therapy. METHODS AND MATERIALS: A retrospective analysis was performed on records of 212 patients with histologically confirmed carcinoma of the vagina treated with irradiation. RESULTS: Tumor stage was the most significant prognostic factor; actuarial 10-year disease-free survival was 94% for Stage 0 (20 patients), 80% for Stage I (59 patients), 55% for Stage IIA (63 patients), 35% for Stage IIB (34 patients), 38% for Stage III (20 patients), and 0% for Stage IV (15 patients). All in situ lesions except one were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence; most of them received interstitial or intracavitary therapy or both, and the addition of external-beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) and IIB (parametrial involvement) 66% and 56% of the tumors, respectively, were controlled with a combination of brachytherapy and external-beam irradiation; 13 of 20 (65%) Stage III tumors were controlled in the pelvis. Four patients with Stage IV disease (27%) had no recurrence in the pelvis. The total incidence of distant metastases was 13% in Stage I, 30% in Stage IIA, 52% in Stage IIB, 50% in Stage III, and 47% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was of relative importance in achieving successful results. In patients with Stage I disease, brachytherapy alone achieved the same local tumor control (80-100%) as in patients receiving external pelvic irradiation (78-100%) as well. In Stage II and III there was a trend toward better tumor control (57-80%) with combined external irradiation and brachytherapy than with the latter alone (33-50%) (p = 0.42). The incidence of grade 2-3 complications (12%) correlated with the stage of the tumor and type of treatment given. CONCLUSION: Radiation therapy is an effective treatment for patients with vaginal carcinoma, particularly Stage I. More effective irradiation techniques, including optimization of dose distribution combining external irradiation and interstitial brachytherapy in tumors beyond Stage I, are necessary to enhance locoregional tumor control. The high incidence of distant metastases emphasizes the need for earlier diagnosis and effective systemic cytotoxic agents to improve survival in these patients.     

Long-term follow-up in radiation therapy of carcinoma of the vagina

A retrospective analysis of 134 patients with histologically confirmed carcinoma of the vagina is reported. Actuarial disease free 5-year survival was: Stage 0 (15 patients), 90%; I (39 patients), 90%; IIA (39 patients), 58%; IIB (21 patients), 32%; III (12 patients), 40%; IV (8 patients), 0%. Fifteen patients had carcinoma in situ; of these, 14 were controlled with interstitial or intracavitary therapy. Of 39 patients with Stage I carcinoma, 37 (95%) showed no evidence of vaginal or pelvic recurrence. Most of them received interstitial or intracavitary therapy or both; the addition of external beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) 22 of 34 (64.7%) patients were controlled with a combination of brachytherapy and external beam irradiation; only two of five (40%) treated with brachytherapy alone exhibited tumor control in the pelvis. Eight of 12 Stage III tumors were controlled in the pelvis. Only two of eight patients with Stage IV had no recurrence in the pelvis even with relatively high doses of irradiation. The dose of irradiation delivered to the primary tumor or the parametrial extension was critical in achieving successful results. The incidence of complications (9.7%) is correlated with the stage of the tumor and type of treatment given.     

Split-course versus continuous pelvis irradiation in carcinoma of the uterine cervix: a prospective randomized clinical trial of the Radiation Therapy Oncology Group

In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. In both groups the external pelvis irradiation was followed by intracavitary brachytherapy in the uterus and vagina, with tandem-colpostat or tandem only, for a dose of 3000 rad at point A for the former, or at 2 cm from the center of the linear source for the latter. In cases where brachytherapy was not possible, a boost of external irradiation with reduced field, with a dose of 1600 rad (200 X 8) was advised. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reactions, and survival. In the entire study population the estimated tumor control in the pelvis at two years after initiation of therapy was: 81% for Stage II-B, 67% for III-A, 53% for Stage III-B, and 32% for Stage IV-A. The estimated two-year survival was: 70% for Stage II-B, 58% for III-A, 46% for III-B, and 23% for IV-A.     

Stage I, grade III adenocarcinoma of the endometrium treated with surgery and irradiation. Sites of failure and correlation of failure rate with irradiation technique

Eighty-three patients treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) and adjuvant irradiation for Stage I, grade III adenocarcinoma of the endometrium were reviewed. At 5 years, the overall survival was 71%, and the disease-free survival (excluding patients dying of intercurrent disease) was 79%. The failure rates for pelvis alone, pelvis plus distant, and distant alone were 4.8%, 4.8%, and 10.8%, respectively. The most common site of failure was the upper abdomen; 12% of all patients had a failure at this site, either alone or in conjunction with failure at another site. The 24% rate of failure in 50 patients receiving a preoperative implant and external irradiation was not significantly different from the 15% failure rate in 33 patients whose adjuvant irradiation consisted of a preoperative implant only. For the patients who had both an implant and external irradiation, the dose of external irradiation had no correlation with the rate of failure. In contrast, the number of milligram-hours delivered to the uterus by the preoperative implant had a strong inverse correlation with the rate of failure, both for patients receiving an implant only and for those receiving an implant plus external irradiation. The data suggest the following: (1) a high-intensity preoperative uterine implant may be an important adjunct to surgery; and (2) external pelvic irradiation in addition to the implant does not seem to be any more beneficial than an implant alone.     

Is long-term survival possible with external beam irradiation for stage D1 adenocarcinoma of the prostate?

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.     

Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival.     

Angiosarcoma of the vagina: a clinicopathologic report. A reappraisal of the radiation treatment of angiosarcomas of the female genital tract

A first case of angiosarcoma of the vagina is described. Review of medical literature fails to show any documented cases of primary angiosarcoma of the vagina. Because of its rarity, no definite treatment could be suggested. The guideline for the management of this disease can only be drawn from several previously reported angiosarcomas of the uterus, cervix, and pelvis. It is recommended that a combined form of external irradiation and intracavitary brachytherapy be used after removal of the tumor.     

Preoperative radiation therapy and surgery in the treatment of "bulky" squamous cell carcinoma of the uterine cervix (stage Ib, IIa, and IIb operable tumors).

Forty-two women with "bulky" squamous cell carcinoma of the uterine cervix, larger than 5 cm, were treated between 1982 and 1988. The median follow-up was 5 years (from 37 to 106 months). The age range was from 25 to 77 years (mean: 49). There were 14 stage Ib, 5 stage IIa, and 23 stage IIb operable patients. Forty grays were delivered at mid-plane of the pelvis (23 fractions in 31 days) using the four-field technique (6-18 MV). External beam radiation therapy was followed by 20 Gy of intracavitary radiation therapy. Forty-eight days later total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and bilateral pelvic lymphadenectomy were performed. The 3- and 5-year disease-free survival was 83 and 81%, respectively. The 5-year locoregional control rate was 83%. Thirteen patients suffered from mild to severe complications (31%) but there were only two long-term (5%) complications.     

Effects of irradiation on mixed müllerian tumors of the uterus.

A retrospective study of 54 patients with histologically proven malignant mixed müllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed müllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.     

An analysis of the severe complications of irradiation of carcinoma of the uterine cervix: treatment with intracavitary radium and parametrial irradiation

Between January 1967 and December 1974, 254 patients with carcinoma of the uterine cervix were treated with either intracavitary radium and parametrial irradiation or 2000 rad whole pelvis irradiation followed by intracavitary radium and parametrial irradiation. In general, these patients had tumors of relatively limited volume and vaginal and uterine anatomy that was favorable for intracavitary radium. Not all patients had a lymphangiogram performed prior to irradiation. Of those who did, only patients with negative lymphangiograms are included in this analysis. All patient had a minimum follow-up of four years. The absolute four year survival rate for this group of patients was 86%. Only 6.3% of patients died of disease. The incidence of severe complications was 7.5%. Complications were associated with a high number of milligram hours of radium plus a high dose of external irradiation, in combination with either asymmetry of the radium system and/or history of previous pelvic inflammatory disease, pelvic surgery, or diverticulosis.     

Influence of preoperative irradiation on failures of endometrial carcinoma with high risk of lymph node metastasis

From 1965-1980, 80 patients with adenocarcinoma of the endometrium, FIGO-AJC Stage I, Grade 3 and Stage II received preoperative radiation therapy. Thirty-three patients had Stage I, Grade 3 and 47 had Stage II. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. They were followed from 3-18 years (median, 6.2 years) after the completion of treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 75%. Preoperative external whole pelvic plus intracavitary irradiation gave the best 5-year survival of 83%; there were no failures after 20 months. In comparison to this group, survival for the intracavitary alone group was 64% at 5 years and 54% at 8 years. The 5-year survival of Stage II was 81% compared to 66% of the Stage I, Grade 3 group. Prognostic variables were analyzed and showed that the residual tumor in the specimen at the time of surgery after the preoperative irradiation was significantly correlated to a worse prognosis: patients who were found to have no residual tumor had a 5-year survival rate of 96% compared to 65% of those who were found to have residual tumor (p less than 0.01). Age, stage, methods of preoperative irradiation, dose of external pelvic irradiation or intracavitary application were not statistically significant prognostic factors. The grade of the tumor was suggestive as a prognostic variable. The most common failure site was the para-aortic lymph nodes independent of treatment methods and stage. Four patients developed complications possibly related to the radiation therapy. Our study suggests that preoperative external and intracavitary irradiation reduces the frequency of residual microscopic carcinoma and improves survival for patients with Stage I, Grade 3 and Stage II carcinoma of the endometrium.