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.     

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial

BACKGROUND: This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma. METHODS: From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR. RESULTS: The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant. CONCLUSIONS: The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR.     

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.     

External radiation therapy of stage I cancer of the endometrium: a need for reappraisal of this adjunctive modality

One hundred and eighty-five patients with Stage I cancer of the endometrium were irradiated preoperatively. All were irradiated to the whole pelvis by external beam only using supermegavoltage apparati. The total mid-pelvis dose ranged from 4500 cGy/5 weeks to 5500 cGy/6 1/2 weeks. Surgery followed usually in 6 weeks. Complications were minimal. Disease-free survival at Stage IA was 92.4% 5-year, 87.7% 10-year; Stage IB was 83.5% 5-year, 74.6% 10-year. Prognosis was related to stage, grade, depth of myometrial penetration, the presence of "residual" tumor at hysterectomy. External beam preoperative irradiation is recommended for all Stage I patients; Stage IB with higher grade pathology should have intracavitary irradiation supplemental to the external irradiation.     

Stage II carcinoma of the endometrium: results of therapy and prognostic factors

A retrospective analysis is reported of 116 patients with Stage II carcinoma of the endometrium treated definitively with combined radiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) or irradiation alone from January 1960 through December 1981. At 5 and 10 years, the overall survival for all patients was 71 and 52% and the disease-free survival was 73 and 69%, respectively. Of 90 patients in the combined therapy group, most received a preoperative intracavitary insertion (3500 mgh to the uterus and 2000 mgh to the upper vagina) and preoperative external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria, with midline shield) followed in 4 to 6 weeks by a TAH-BSO. The 5 and 10 year disease-free survival for this group was 78 and 75%, respectively. The incidence of major complications was 7% for the combined therapy group. Twenty-six patients were treated with irradiation alone; most of them received two intracavitary insertions (5000 mgh to the uterus and 3000 mgh to the upper vagina) and external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria). The 5 and 10 year disease-free survival was 53 and 45%, respectively. The incidence of major complications was 19%. Factors found to influence the prognosis were histologic grade of tumor, clinical and histologic degree of tumor involvement of the ectocervix, presence of residual tumor in the hysterectomy specimen and the depth of myometrial invasion.     

Prognostic assessment of tumor regression after external irradiation for cervical cancer.

From February 1980 to December 1986, 428 cases of cervical cancer in Stage I through IVA were given curative radiation therapy at Chang Gung Memorial Hospital, Taipei. All of them received external irradiation and intracavitary brachytherapy. The degree of tumor regression was assessed immediately before the first intracavitary brachytherapy treatment. Patients were classified at this time as having (a) no gross residual tumor, or (b) gross residual tumor. Factors found to be associated with tumor regression by logistic regression analysis were stage, age and hemoglobin level. Patients with advanced cancer (Stage III, IVA), young age (less than 40 years), and low hemoglobin level (less than 10 g/dl) had a low incidence of no gross residual tumor. Five-year survival rate was 77% in patients with no gross residual tumor and 31% in patients with gross residual tumor (p less than 0.001). This significant difference held true even when one compared these two groups stage for stage; the difference was 77% versus 41% (p less than 0.001) in Stage II and 72% versus 28% (p less than 0.001) in Stage III. The local relapse rate was 59% in the gross residual tumor groups, significantly greater (p less than 0.001) than the 12% found in the no gross residual tumor group. It was concluded that patients whose tumors did not regress after external pelvic irradiation tended to recur after intracavitary brachytherapy, most often locally. This would justify a more aggressive treatment to improve local tumor control in this subset of high risk patients.     

子宫内膜癌单纯放射治疗回顾性分析

90 patients with endometrial carcinoma treated from 1958 to 1984 by radiotherapy alone are presented. They constituted 18.7% of all cases of endometrial carcinoma treated in the same period. According to the clinical staging system of FIGO, there were 28.89% Stage Ia, 8.89% Stage Ib, 38.89% Stage II, 20% Stage III and 3.33% Stage IV lesions. In this series, 82 patients suffered from adenocarcinoma and 8 patients from adenoacanthoma. Two treatment regimens were adopted: 1. intracavitary Ra (137Cs or 60Co) as the major form of treatment supplemented by external irradiation in 82 patients (including 5 by intracavitary 137Cs afterloading), 2. external irradiation supplemented by intracavitary Ra (or 137Cs) radiation in 8 patients. The overall 5-year survival rate was 48.89% (Stage I 58.82%, Stage II 51.42%, Stage III 33.3% and Stage IV 0%). Complications were proctitis in 17 cases hematuria in 4 and rectovaginal fistula in 1. The 5 patients treated by intracavitary afterloading radiation with high doses at reference points A and F all survived for more than 5 years. This may imply a bright future for this form of radiotherapy in the treatment of endometrial carcinoma.     

High dose-rate afterloading in the treatment of cervical cancer of the uterus

From January 1981 to December 1983, 380 patients with cervical carcinoma of uterus were treated with high dose-rate intracavitary afterloading therapy (Ralstron-20B) and 60Co external irradiation. All of these cases have been followed over 3-5 years. The 5-year survival rates for Stages I, II, III, and IV were 100%, 81.5%, 73.9%, and 0% respectively. The over all 5-year survival rate was 79.1%. The results were comparable to that of conventional radium therapy in 1980 (5-year survival rate for radium group: Stage I 50%, Stage II 72.2%, Stage III 52.2%, Stage IV 0%). The moderate and severe rectal reactions in this series were 11.8% and 1.6% (radium group moderate 6.0%, severe 2.2%), which were higher than that of radium group. The incidence of bladder reaction was 7.1%. The problems of high dose-rate intracavitary therapy and the combination therapy with intracavitary and external irradiation are discussed in this paper.     

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)     

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.     

Lack of effect of tumor size on the prognosis of carcinoma of the uterine cervix Stage IB and IIA treated with preoperative irradiation and surgery.

PURPOSE: The purpose of this analysis was to evaluate the prognostic significance of cervical tumor size in patients with Stages Ib and IIa carcinoma of the cervix treated with preoperative irradiation and radical or conservative hysterectomy. METHODS AND MATERIALS: This study is a retrospective analysis of 177 patients. One hundred forty-one patients had Stage Ib and 36 patients had Stage IIa carcinoma of the cervix. All patients were treated with preoperative irradiation and surgery. Radiation therapy consisted of external pelvic irradiation and intracavitary brachytherapy; total doses ranged from 30 to 60 Gy to the pelvic sidewall and 60 to 70 Gy to point A. Surgery consisting of radical hysterectomy and lymph node dissection or a conservative hysterectomy and lymph node dissection was performed 4 to 6 weeks after completion of irradiation. RESULTS: The 5-year progression-free survivals were 80% for Stage Ib and 63% for Stage IIa (p = 0.03). The 5-year cumulative pelvic failure rates for Stage Ib were 16% for tumors <3 cm and 9% for tumors >3 cm (p = 0.90). The 5-year cumulative pelvic failure rates for Stage IIa were 22% for tumors <3 cm and 22% for tumors >3 cm (p = 0.75). The corresponding cumulative distant metastasis failure rates at 5 years for Stage Ib were 21% for tumors <3 cm and 21% for tumors >3 cm (p = 0.60). For patients with Stage IIa disease, the 5-year cumulative distant metastasis rates were 33% for tumors <3 cm and 36% for tumors >3 cm (p = 0.70). A multivariate analysis was performed to evaluate prognostic factors for the endpoint of progression-free survival. The variables that were analyzed were patient age, tumor histology, tumor size, clinical stage, point A and pelvic lymph node irradiation dose, and cervical tumor status and pelvic lymph node status at the time of hysterectomy. The variables that were found to be of independent significance for progression-free survival by multivariate analysis were pelvic lymph node irradiation dose (p <0.001), pelvic lymph node status at the time of hysterectomy (p = 0.01), and clinical stage (p = 0.02). Cervical tumor size at the time of diagnosis and the presence of tumor cells in the cervix in the hysterectomy specimen was not an independent prognostic factor by multivariate analysis. The overall severe complication rate was 11% for all patients. CONCLUSIONS: For this population of patients treated with preoperative irradiation and surgery, pelvic lymph node status at the time of hysterectomy and the preoperative irradiation dose to the pelvic lymph nodes are independent predictors of progression-free survival and the development of distant metastasis. The pretreatment cervical tumor size is of less importance for predicting progression-free survival and the development of distant metastasis but clinical stage is an important prognostic variable. These results are in contrast with those of surgery or irradiation alone, in which primary tumor size is a critical prognostic factor for all outcome parameters.     

High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients

Purpose: To report the results of radiation therapy in carcinoma of the cervix treated by external irradiation and high-dose-rate (HDR) intracavitary brachytherapy.

Methods and Materials: This is a retrospective analysis of 2063 patients with histologically proven carcinoma of the cervix treated by external irradiation and HDR intracavitary brachytherapy between March 1985–December 1991. The Kaplan-Meier method was used for survival and disease-free survival analysis. Late complications in the bowel and bladder were calculated actuarially.

Results: There were 71 patients who did not complete the course of irradiation so only 1992 patients were retrospectively analyzed for survival. There were 2 patients (0.1%) in Stage IA, 211 (10.2%) Stage IB, 225 (10.9%) in Stage IIA, 902 (43.7%) in Stage IIB, 14 (0.7%) in Stage IIIA, 675 (32.7%) in Stage IIIB, 16 (0.8%) in Stage IVA, and 16 (0.8%) in Stage IVB. The median follow-up time was 96 months. The actuarial 5-year disease-free survival rate was 79.5%, 70.0%, 59.4%, 46.1%, 32.3%, 7.8%, and 23.1% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. The actuarial 5-year disease-free survival rate for Stage IB₁ and IB₂ squamous cell carcinoma was 88.7% and 67.0%. The actuarial 5-year overall survival rate was 86.3%, 81.1%, 73.0%, 50.3%, 47.8%, 7.8%, and 30.8% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. Pattern of failure revealed 20.8% local recurrence, 18.7% distant metastases, and 4% in both. The late complication rate Grade 3 and 4 (RTOG) for bowel and bladder combined was 7.0% with 1.9% Grade 4.

Conclusion: HDR brachytherapy used in this series produced pelvic control and survival rates comparable to other LDR series.     

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.     

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.     

External cobalt 60 irradiation alone for stage IIB carcinoma of the uterine cervix

From 1964 to 1980, 97 patients with Stage IIb carcinoma of cervix uteri were treated by external 60Co irradiation alone. Of these 97 patients, 94 (96.9%) had squamous cell carcinoma. The parametrial extension of the lesion almost reached the pelvic wall in 73.2% and vaginal extension reached to the upper half of vaginal in 24.7% of the patients. A tumor dose of 60 Gy was given to the whole pelvis by a four field technic (opposing parallel AP and lateral portals) in 6-8 weeks. A booster dose of 10 Gy was delivered to the cervix by a pair of reduced opposing parallel AP portals or a perineal portal in a week. The doses delivered were equivalent to the Time-Dose-Fractionation (TDF) value of 110-130 at the center of pelvis and 90-110 in the whole pelvis. The 5-year survival rate for all 97 patients was 56.7%. It was 59.8% when those who died of other diseases were excluded. The prognosis of patients without residual tumor on the cervix and/or vagina was better than that with residual tumor (p less than 0.01). Thirty-seven patients died of cancer (23 died of recurrence, 8 of distant metastases, 2 of both, and 4 were lost before the fifth year). Of these 37 patients, 97.3% died within 3 years after initial treatment. During the radiation treatment, reactions were moderate. Late complications included 19 (19.6%) with mild cystitis and 16 (16.5%) with mild proctitis, 2 (2.7%) developed recto-vaginal fistula. These results were slightly poorer than those using intracavitary and external irradiation or the combination of preoperative irradiation plus surgery. Yet, for patients with extensions nearing the pelvic wall or with contra-indications to surgery or intracavitary radiotherapy, external irradiation alone is still of value.     

Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes

Purpose: To evaluate local tumor control, cause-specific survival, patterns of relapse, and toxicity in patients with cervical cancer and positive para-aortic lymph nodes treated with radiation therapy alone.Methods: This is a retrospective chart review of 43 patients with cervical cancer and biopsy-proven positive para-aortic lymph nodes treated with radiation therapy treated from 1965 to 1993. There were 15 patients with clinical Stage I disease, 12 with Stage II, and 16 with Stage III. Patients were treated with external irradiation to the pelvis and para-aortic regions combined with brachytherapy. None received chemotherapy.Results: The 5-year overall survival rate was 32% and the median overall survival was 2.2 years. The 5-year cause-specific survival rate was 49% and the median cause-specific survival was 2.7 years. The cause-specific survivals at 5 years were 47% for Stage I, 64% for Stage II, and 46% for Stage III. Tumor recurrence occurred in 20 patients. The sites of recurrence were in the pelvis only in 3, the pelvis and distant metastasis in 9, and distant metastasis only in 8 patients. Severe, grade 3 complications occurred in 2 patients. One patient developed an enterovaginal fistulas and 1 developed radiation myelitis.Conclusion: Pelvic and para-aortic irradiation and brachytherapy resulted in a 49%, 5-year, cause-specific survival. Clinical tumor stage did not effect outcome. The majority of relapses occurred at distant sites. Toxicity was acceptable. Systemic chemotherapy should be considered as adjunctive therapy for these patients.     

Intracavitary brachytherapy combined with external-beam irradiation for squamous cell carcinoma of the thoracic esophagus.

During the 15 year period from 1974 to 1988, 277 patients with previously untreated, histologically confirmed, squamous cell carcinoma of the thoracic esophagus were treated with the Time Dose and Fractionation (TDF) factor of more than 99. Of these, 161 patients were treated with external beam irradiation combined with intracavitary brachytherapy. Intracavitary brachytherapy was done for all patients for whom insertion of an outer applicator 1 cm in diameter was possible and for whom a relatively good performance status was seen at completion of external beam irradiation. Except for mild radiation-induced esophagitis, no acute radiation injuries were noted. The early clinical effect of radiation upon the esophageal lesion was determined by esophagography and esophagoscopy, approximately 1 month after the combined radiotherapy; a complete response was observed in 86 (53.4%) of the 161 patients. Furthermore, after a 5 year follow-up, local control of esophageal cancer was found to have been successful in 51 (31.7%) of the 161 patients. The highest rate of local control was associated with the following criteria: Stage I, T1, tumor length less than 5 cm, and superficial or tumorous type of tumor. The 5-year actuarial survival rates were 43.3% for Stage I, 21.1% for Stage II, and 0% for both Stages III and IV. Benign radiation-induced esophageal ulcerations or strictures did develop in five of the long-term survivors, suggesting that the dosage is close to the maximal tolerance of the esophagus. We recommend that 1500-2000 cGy in two or three fractions is the optimal dosage for intracavitary radiation of the esophageal mucosa after external irradiation of 5500 cGy in 22 fractions for 5.5 weeks or 6000 cGy in 30 fractions for 6 weeks. We believe that intracavitary treatment of esophageal carcinoma is a highly effective and a safe therapeutic modality, not only as a palliative therapy, but also as a radical treatment for patients in Stages I and II.     

Treatment of stages i and ii cancer of the cervix: Analysis of 5 year survival and recurrence rates

Eight hundred and thirty five patients with a diagnosis of Stages I or II carcinoma of the cervix were treated at Instituto Portugues de Oncologia de Francisco Gentil, in Lisbon, from 2 January 1965 to 30 June 1971. The purpose of this study was to calculate the 5 year survival rates and to analyze the treatment failures according to the modality of treatment applied. Two series of Stages Ib and IIa patients were available; one group was treated with radiotherapy, and the other with radical hysterectomy and pelvic lymphadenectomy after previous intracavitary radiumtherapy. No statistically significant difference was found in the 5 year survival of both groups. Most Stage IIb patients were treated with radiotherapy.When residual tumor was found in the uterus of patients who underwent radical surgery after intracavitary radiumtherapy it did not influence survival. On the other hand, the presence of metastatic pelvic lymph nodes after intracavitary radium treatment was related to a lowered survival rate. The number of severe injuries was higher in patients who were treated surgically. Recurrences developed within 5 years after completion of treatment in 10.8% of Stage Ib patients, 21.5% of Stage IIa patients, and 34.5% of Stage IIb patients. Ninety per cent of these recurrences appeared within 3 years after therapy.     

Long-term follow-up of RTOG 88-05: twice-daily external irradiation with brachytherapy for carcinoma of the cervix

PURPOSE: To evaluate the efficacy and toxicity of twice-daily external irradiation to the pelvis with brachytherapy for carcinoma of the cervix in a long-term follow-up study. METHODS AND MATERIALS: This study was designed to administer twice-daily irradiation doses of 1.2 Gy to the pelvis, 5 d/wk. Radiotherapy also included one or two low-dose-rate intracavitary implants, to deliver a total minimal dose of 85 Gy to point A and 65 Gy to the lateral pelvic lymph nodes. RESULTS: Eighty-one patients with clinical Stage IB-IVA carcinoma of the cervix were enrolled in this prospective, single arm, Phase I/II study. Hyperfractionated irradiation was completed in 88%. Brachytherapy was given in two implants in 46% and in one implant in 54%. Six patients had acute Grade 3 toxicities. The cumulative rate of Grade 3 and 4 late effects for patients with Stage IB2, IIA, and IIB disease was 7% at 3 years, 7% at 5 years, and 10% at 8 years. For patients with Stage III and IVA disease, the rate of late toxicities (Grades 3 and 4) was 7% at 3 years and 12% at 5 years. The site of first failure was in the pelvis in 41%, para-aortic or supraclavicular lymph nodes in 6%, and other distant metastatic sites in 14%. The absolute survival rate was 61% at 3 years, 48% at 5 years, and 45% at 8 years. The disease-free survival rate was 43% at 3 years, 38% at 5 years, and 33% at 8 years. CONCLUSION: The results suggest that, combined with brachytherapy, hyperfractionated irradiation to total parametrial doses about 10% greater than doses administered with standard fractionation pelvic irradiation was tolerated and at least appears to be as effective as standard fractionation pelvic irradiation.     

Carcinoma of the endometrium results of treatment

From 1955 to 1974, 294 patients with primary carcinoma of the endometrium were treated by a combination of preoperative irradiation and surgery or by irradiation alone. Of these 294 patients, 12 had biopsy-proven involvement of the cervix. The current FIGO classification was used. The overall 5-year survival was 79%. The 5-year survival for Stage I, II, and III was 83%, 91%, and 40% respectively. The 5-year survival was 88% for operable Stage I carcinoma of the endometrium and 65% for inoperable Stage I. One hundred ninety-six patients with operable Stage I carcinoma of the endometrium received preoperative irradiation followed by total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) and were studied in greater detail. In this group, the incidence of sterilization and the degree of myometrial invasion in the removed uterus were important factors in determining the prognosis. Preoperative radium yielded better results than preoperative external irradiation.