Preoperative radiotherapy and surgery for endometrial carcinoma: prognostic significance of the sterilization of the specimen.

INTRODUCTION: We report a retrospective study on the analysis of the operative specimen after preoperative radiotherapy for FIGO (1971) stage I or II endometrial carcinoma. METHODS AND MATERIALS: From 1976 to 1996, 221 patients were treated with external radiotherapy (XRT) and/or low-dose-rate brachytherapy (BT) followed by surgery (S). Patients with cervical involvement (89 patients) or with high-grade tumors (49 patients) received XRT and BT. Patients stage FIGO Ia (89 patients) or with low-grade tumors (57 patients) received BT alone. Surgery was performed 5 to 6 weeks after irradiation. RESULTS: The mean follow-up is 78 months (12-216). The 5-year survival was 90% for FIGO Ia, 80% for FIGO Ib, and 84% for FIGO II (p = 0.51). According to the differentiation, 5-year survival was 87% for grade 1, 84% for grade 2, 84% for grade 3 (p = 0.10). Grade 3 complications were registered in 2% (no grade 4). The tumors were sterilized in 37 patients (17%), sterilized but with dystrophic glands in 34 patients (16%), only modified and altered in 21 patients (9.5%), with viable cells in 56 patients (26%). After preoperative radiotherapy, 37/148 specimens were sterilized (25%), 14/74 after brachytherapy and surgery (19%), 23/74 after external radiotherapy-brachytherapy and surgery (31%). According to the response of the specimen, 5-year survival was 87% when the tumor was sterilized, 96% when altered glands were present, 85% when modified, and 76% if residual tumor with viable cells was identified (p = 0.043). CONCLUSION: Preoperative radiotherapy followed by surgery is a safe and effective treatment of FIGO stage I or II endometrial carcinomas. BT with two uterine tubes seems to be of interest in the contribution of the treatment of the uterus to sterilize the specimen. The analysis of this new prognostic factor remains important to select a population with worst prognosis.

Conservative management of rectal adenocarcinoma by radiotherapy.

PURPOSE: The aim of this study was to analyze the experience of Centre GF Leclerc for conservative and curative treatment by radiotherapy of low rectal cancer. PATIENTS AND METHODS: A total of 151 patients received radiotherapy alone for rectal adenocarcinoma with curative intent. They were clinically staged according to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US) has been used systematically, compared with computed tomographic scan and magnetic resonance imaging when needed. Intracavitary contact X ray was given to 129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was used in 34 cases (22.5%). RESULTS: Complete response was obtained in 93%. Local failures were observed in 50 cases (28%); two occurred in pelvic nodes after intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility significantly influenced the rate of local failure (p=0.009 and 0.007). The addition of external radiotherapy in patients with poor prognostic factors improved the local control rate. A total of 39 patients with recurrence were amenable to salvage surgery. After salvage treatment, the local control rate was 82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a specific survival of 66%. There was no difference in local control or survival according to differentiation of the tumors and distance between anal margin and the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter function was judged to normal in 102 of 104 patients (98%). CONCLUSION: Intracavitary contact X ray is the treatment of choice for clinical Stage T1A rectal tumors. External radiotherapy significantly improved the results of treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a safe selection of indications. Radiotherapy alone may be proposed for selected cases as an alternative to mutilating surgery for small rectal adenocarcinoma.

Organ preservation in cervix cancer.

From 1970 to 1994, 642 patients with carcinomas of intact uterine cervix were treated with radiotherapy alone Univariate and multivariate analysis was carried out of predictive factors for: 1) pelvic control and survival rates; 2) complications using French-Italian Syllabus, combined with an evaluation of the impact of customized treatment planning policy (CTP) on G3-G4. According to Figo substaging 30% of patients were stage I, 42% stage II and 28% stage III/IV. Diameter of cervical disease was 3-5 cm in 38% of cases and > 5 cm in 15%. Nodal involvement from lymphangiogram was 21%. The distribution of sequelae and complications was: G1 23%, G2 18%, G3 6%, G4 2.5%. The distribution of G3-G4 per organ was: genitalia 6% (no G4), rectum 4%, colon 1.5%, bladder 1.2%, soft tissues 1%, small bowel 0.5%. Stage (RR ranging from 1.5 for stage IIb to 5 for stage III/IV), tumor size (RR = 1.5), nodal involvement (RR = 2) were significant predictive factors for survival and pelvic control rates (p < 0.0001). In univariate analysis the main factors influencing the risk of G3-G4 complications were: Figo substaging, external radiation dose over 40 Gy (ED), parametrium boost (PB), use of brachytherapy vaginal cylinders applicator (CA), high HWT and mean rectal dose rate for rectal complications. In multivariate analysis, CA remained the only predictive factor for G3-G4 bladder events (odds ratio OR = 10.8) while the increase of mean dose rate (OR = 1.1), use of CA (OR = 4.2) and ED > 40 Gy (OR = 4.4) were predictive of severe rectal sequelae. Prevention of complications based upon individual changes of treatment planning according to dosimetry parameters led to a sharp decrease in severe complications with time. No G4 occurred after 1983. G3 rates dropped from 5% before 1978 to 0% after 1983 in stage I, from 10% to 6% in stage II and from 23% to 12% in stages III/IV. Meanwhile 5-year LC rates remained stable in early stages, about 91% in stage I and 85% in stage II, conversely they fell from 75% to 55% in stages III/IV, thus raising the problem of underdosage and/or more reliable staging with time. It is concluded that radiotherapy prescriptions based upon tumor diameter per stage and delivered using CTP led to an eradication of lethal complications and provided significant decrease of G3 in all cases while maintaining high cure rates in early stages. Dose reduction should be considered with caution in stages III/IV.

Preoperative radiotherapy in stage I/II endometrial adenocarcinoma.

From 1972 to 1993, 170 patients received preoperative radiotherapy followed, 5-6 weeks later, by total extrafascial hysterectomy with bilateral salpingo-oophorectomy without lymphadenectomy. Eighty-three patients with good prognostic factors (low grade tumour and no cervical involvement) received low dose rate utero vaginal brachytherapy alone before surgery (Group 1). Eighty-seven patients with poor prognostic factors (high grade tumors and/or cervical involvement) received external radiotherapy to 40 Gy and low dose rate brachytherapy before surgery (Group 2). A single vaginal failure was observed (0.6%). The overall pelvic failure rate was 2.3% (four patients) including two cases with pelvic recurrence and metastases. Three of the four pelvic failures occurred in Group 1. Using the 1971 FIGO clinical staging, 5-year disease-free survival was 82% in Stage Ia, 79% in Stage Ib, and 81% in Stage II (P = 0.36). Five-year disease-free survival was 86% in Grade 1, 76% in Grade 2, and 83% in Grade 3 (P = 0.20). Five-year overall survival was 83% in Stage Ia, 79% in Stage Ib, and 83% in Stage II (P = 0.78). Five-year overall survival was 88% in Grade 1, 77% in Grade 2,83% in Grade 3 (P = 0.27). Complications were recorded with the French-Italian syllabus. Grade 2 complications occurred in 12 cases (7%), Grade 3 in five cases (3%). The lack of correlation between classical risk factors (stage, grade) and disease outcome suggests that preoperative radiotherapy strategies should be preferred when such factors can be identified before surgery.

Maximum and mean bladder dose defined from ultrasonography. Comparison with the ICRU reference in gynaecological brachytherapy.

The reference bladder dose for gynaecological intracavitary brachytherapy (BT), as defined by the ICRU 38 Report, is often criticised as it is seldom representative of the highest bladder dose nor it gives an idea of the area exposed to a significant dose. Since November 1990, ultrasound measurements are routinely made in order to determine the actual dose delivered to the bladder of each patient. The technique was as follows. (1) the bladder is filled up with 150-200 cm3 of sterile isotonic saline. (2) The intrauterine position of the tube is checked. (3) The bladder anatomy is controlled. (4) Points of measurements are identified: ICRU bladder reference, minimum distance between bladder mucosa, uterine tube and other similar measurements taken every 15 mm along the radio-active line. Maximum and mean doses are calculated at the sagittal plane. Measurements are performed by moving the transducer along the skin of the patient and included in the calculation of dose distribution. Doses delivered to each relevant point are compared. This enables determination to be made of the differences between the ICRU and the doses actually observed at the bladder wall with aid of ultrasonography. BT applications were checked in 58 patients (69 measurements). The method was feasible in all cases. The comparison between ICRU dose from orthogonal films and the ICRU dose from ultrasonography resulted in a 90% accuracy. The maximum and mean doses for utero-vaginal BT are higher than the ICRU dose in 75% of cases (range, 2-8). Measurements are now abandoned for vaginal applications as the ICRU dose only could be measured.(ABSTRACT TRUNCATED AT 250 WORDS)

The Dijon clinical staging system for early rectal carcinomas amenable to intracavitary treatment techniques.

The Dijon clinical and endoscopic staging system for intracavitary radiotherapy of rectal cancer takes into account the size and the depth of penetration of the rectal wall. Its prognostic value was evaluated in a series of 72 patients with rectal adenocarcinoma treated at the Centre de Lutte Contre le Cancer G. F. Leclerc in Dijon: 30 presented with a clinical stage (CS) T1A (purely exophytic tumors of less than 3 cm). The 5-year local relapse-free actuarial survival (LRFS) was 97%. Fourteen patients with CS T1B (infiltrative component and less than 3 cm diameter) had a LRFS of 77%. Nine patients with CS T2A tumors (with larger exophytic tumors) has a LRFS of 65%. Nineteen CS T2B cases (larger than 3 cm with an infiltrative component) presented a LRFS of 60%. The size of the tumor and the clinical estimate of the infiltration of the rectal wall both have a significant prognostic value: adenocarcinoma of less than 3 cm (n = 44) had a LRFS of 93% versus 59% in larger ones (n = 39; p = less than 0.01). Free mobile lesions (n = 39) did better (n = 33; LRFS = 86%) than infiltrated tumors (n = 33; LRFS = 66%; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in limited rectal cancer treated with intracavitary irradiation.

At the Centre Georges-François Leclerc of Dijon, 91 limited rectal tumors received a complete intracavitary 50 kV contact radiotherapy alone or associated with interstitial brachytherapy according to the guidelines of J. Papillon. Nineteen had a villous adenoma and 72 a well or moderately differentiated rectal adenocarcinoma. The majority of patients had contra-indications for major surgical procedures. The median age was 70 years. Seventy-six percent (69/91) of the rectal tumors remained free from local recurrence. After salvage therapy, the local control was 91% (83/91). Sphincter preservation was obtained in 85% (77/91). "De novo" adenocarcinomas developed on pre-existing benign pathology and villous adenomas were not significantly different with regard to local control (76% resp. 75% versus 59.5%; p = 0.22). According to the Dijon clinical staging system, the local relapse-free survival at 5 years was 97% for CS T1A, 77% for CS T1B, 65% for CS T2A, and 60% for CS T2B. Tumors of the anterior rectal wall had a better local control rate than lateral and posterior primaries (100% versus 63% versus 67%). For the middle rectum, the local relapse-free survival was 94% compared to 54% of the upper and 77% of the lower rectum. Four additional patients had a preoperative intracavitary therapy and salvage surgery for incomplete tumor regression; the complete remission rate is 96% (91/95). Intracavitary radiotherapy alone is an effective treatment for limited rectal cancers. Contact X ray therapy can be used alone in CS T1A whereas a combination of contact X ray therapy and interstitial brachytherapy is often the optimal approach in CS T1B and CS T2A. In CS T2B, our data do not support the use of intracavitary techniques alone. In these cases, the sequence external irradiation followed by an interstitial implant seems of interest and deserves further evaluation with more patients and follow-up.