[Treatment of breast cancer: its progress and its limits]. / Le traitement du cancer du sein: ses progrès et ses limites.

Conservative surgical treatment has replaced mastectomy in the treatment of many breast cancers in the first clinical stages. This treatment introduces the risk of local recurrences which should always be prevented by radiotherapy. A better local control after conservative treatment or mastectomy might increase the cure rate. However, this is still open to controversy. In the case of more locally advanced tumors, a neoadjuvant chemotherapy decreases the risks of local recurrences but does not improve survival. The benefit of medical adjuvant treatment presented up to 10 and 15 years in the meta-analysis are reserved. The nature of the benefit, short delay in additional survival or cure of some patients is discussed. The effects of chemotherapy are most likely partly secondary to an action on the ovaries since the results are much more apparent in premenopausal patients. Comparative trials with new chemical or biological agents are still necessary. Up to now the benefit brought by the mammographic screening seems to be more important than the therapeutic progress itself.

Carcinoma of the intact uterine cervix treated with radiotherapy alone: a French cooperative study: update and multivariate analysis of prognostics factors.

PURPOSE: To determine independent prognostic factors in a group of 1875 patients with invasive carcinoma of the intact uterine cervix treated with radiotherapy alone in a French cooperative study from 1970 to 1993. MATERIALS AND METHODS: Patients were staged according to the UICC-FIGO and MDAH substaging. The distribution per FIGO stage was Ia-Ib: 25.5%; IIa: 12%; IIb: 29%; IIIa: 5%; IIIb: 25%, and IV: 3.5%. Ninety-two percent had squamous cell carcinoma. The maximum diameter of the clinically detectable cervical disease was less than 3 cm in 24.5% of Stages I-II and in 10% of Stages III-IV, more than 5 cm in 13.5% of Stages I-II, and in 16% of Stages III-IV. Nodal involvement was shown on lymphangiogram in 16% of Stages I-II and in 32.5% of Stages III-IV. RESULTS: 1) Univariate analysis of Stages I and II: stage, cervical disease diameter, and nodal involvement are significant prognostic factors. Five-year specific survival rate (5ySS) is 83.5% in Stage Ib, 81% in IIa and 71% in IIb. Five-year disease-free survival rate (5yDFS) is 86% in tumors less of 3 cm, 76% in tumors of 3 to 5 cm, and 61.5% in tumor larger than 5 cm. Lymphangiogram strongly influences the 5-year pelvic disease-free survival rate (5yPDFS): respectively, 90% in nonpositive lymphangiogram vs. 65% when positive. A significant drop in specific and disease-free survival is observed (10 and 14%, respectively (p = 0.04) when comparing adenocarcinoma and squamous cell carcinoma. Age is a significant prognostic factor for specific survival because patients aged less than 30 years old have 91% vs. about 75% for patients over 30 years (p = 0.03). 2) Univariate analysis of Stages III-IV: Stage and positive lymphangiogram are predictive factors for relapse and death. The MDAH substaging is more reliable to predict the probability of pelvic disease-free survival in Stage III. At 5 years, the FIGO Stages IIIa and IIIb have a rather similar PDFS (65% vs. 59%). Conversely, the difference of survival rates between MDAH Stage IIIA and Stage IIIB is more demonstrative (69% vs. 47.5%). 3) Multivariate analysis (Cox P. H. R. model). Nodal involvement and stage remain significant for all three models in all stages (p < 0.0001). Age above 70 years influences specific survival for Stage I-II (p = 0.01). Tumors larger than 5 cm and adenocarcinoma also appear to be independent prognostic factors for specific and disease-free survival in Stage I-II (p = 0.05 and p = 0.005, respectively). CONCLUSIONS: The relevance of tumor size (less or greater than 4 cm) is now recognized in the 1995 revised FIGO staging in Stage Ib but unfortunately not in other stages. Tumor size per stage and nodal status should be systematically recorded to allow a better prediction of failure rates and to compare literature reports.

Radiation therapy of cervical cancer with dosimetric prevention of late pelvic complications.

Two successive series of invasive carcinoma of the cervix (268 and 307 patients) were treated by radiation alone between 1973 and 1977 and 1978 and 1985. The main difference between these periods was the method used to determine the definitive dose delivered by intracavitary therapy. The treatment in all cases consisted of external and intracavitary radiotherapy. Computerized dosimetry was performed in all patients with determination of dose rate, maximum and mean cumulated doses at the reference points of the rectum and bladder. The tolerance doses to the rectum and bladder previously established and represented graphically were used prospectively for the patients from 1978 to 1985, permitting better coordination of the two treatments. The graph takes into account the fractionated tolerance to external irradiation and intracavitary radiotherapy. The systematic use of this method yielded results at six years for all stages which were comparable from one series to another. Parallel to this, the improvement in the number and gravity of the complications was significant, especially for grade 2 complications (P = 0.001) and, to a lesser degree, for grade 3 and 4 complications (P = 0.04). In conclusion, the respect of tolerance doses to the critical organs close to the principal tumoral volume represents an effective method for optimizing radiotherapeutic treatment for cervical cancer.

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.

Carcinoma of the cervical stump: a review of 213 cases.

From 1970 to 1987, 213 cases of carcinoma of the cervical stump were accrued in a multi-institutional prospective cooperative study. This group accounted for 5.5% of cervical carcinoma diagnosed during the same period. 13 had in situ carcinoma and 200 had invasive carcinoma (96% squamous cell carcinoma, 4% adenocarcinoma). Radiotherapy alone (external and brachytherapy) was given to 77%, brachytherapy and surgery to 15% and surgery alone to 8%). FIGO stage distribution was: I (31%), IIa (15%), IIb (27%), IIIa (5%), IIIb (17%) and IV (5%). Five-year locoregional control per stage was 100% in Ia, 85% in Ib, 82% in IIa, 71% in IIb, 45% in IIIa, 54% in IIIb and 30% in IV. Corrected 5-year survival per stage was 82% in Ib, 78% in IIa, 73% in IIb, 69% in IIIa, 38% in IIIb and 0% in IV. The diameter of disease in stage II strongly influenced the 5-year locoregional control (81% for tumours of less than 3 cm vs. 68% for tumours more than 3 cm). Lymphangiogram was associated with a 44.5% 5-year locoregional control when positive vs. 74% when non-positive. Brachytherapy was advantageous in obtaining locoregional control in patients receiving external irradiation and brachytherapy: 81.5% vs. 38.5% in patients treated with external radiotherapy alone. Surgery was performed only for in situ carcinoma and for part of stages Ia, Ib and IIa. There is no significant difference in locoregional control at equal stage between radiotherapy alone and treatment schemes including surgery. However, lethal complications were observed in 6% of the patients of the surgical group as compared to 0.6% of the patients treated with radiotherapy alone. Radical radiotherapy seems to provide similar results of locoregional control and survival at equal stages in carcinoma of the cervical stump compared to carcinoma developed on an intact uterus. The rate of severe complications reported with the French-Italian glossary is 13% for G3 and 3% for G4, which is close to the observed rate during the same period in our series of radical radiotherapy to the intact uterus.

Cervical and vaginal cancer associated with pessary use.

From 1967 to 1990, 96 previously untreated patients with cervicovaginal cancer associated with a history of vaginal pessary use to control uterovaginal prolapse were referred to eight radiation therapy departments in France. Sixty-eight patients had cervical cancer, and 28 had vaginal cancer. The mean interval between pessary insertion and cancer diagnosis was 18 years, with a range of 1 to 41 years. Most patients received radiation therapy and brachytherapy. Few (5%) had Grade 3 treatment side effects. The overall 5-year relative survival rate was 54%; nonsurvival was related to locoregional recurrence. Because almost all tumors occurred at the site of pessary insertion, foreign body chronic inflammation in association with viral infection may be the cause of the tumors.

Exclusive radical radiation therapy in breast carcinoma.

We present the results of 186 breast cancer patients treated initially for locoregional disease by radiotherapy alone, combining cobalt therapy with external electron beam or interstitial iridium implants. According to the TNM classification, the patients were distributed as follows: 3 T1N0, 2 T1N1, 33 T2N0, 36 T2N1, 16 T3N0, 26 T3N1, 6 T3N2, 14 T4N0, 29 T4N1, 9 T4N2 and 12 T4N3. The 5- and 10-year survival rates (52.7% and 36.5%, respectively, for all patients) were directly correlated with the size and location of the breast tumor, and the extent of lymph node involvement. Locoregional recurrence was observed in 39.8% of the cases, metastasis alone in 26.8% of the cases, and a combination of local recurrence and distant metastasis in 14.5% of the cases. The local recurrences and metastases were directly correlated with the extent of locoregional involvement. Late complications and sequelae were mostly minor and occurred in less than 25% of the cases; severe sequelae occurred in no more than 2% of the cases. They depended on the initial tumor volume and the tumor dose. Our results, along with those in the literature, indicate that radiotherapy administered alone is a valid therapeutic option in breast cancer.

Tumorectomy and radiation therapy in early breast cancer: a report on 392 patients.

Three hundred ninety-two breast cancer patients (231 with stage I and 161 with stage II disease) were treated with tumorectomy followed by radiation therapy. The overall actuarial survival rate was 86.5% at 5 years and 78.0% at 10 years. The 5-year disease-free survival rate was 70.2%. Survival rates depended on locoregional tumor extension. Patients with stage I tumors had a survival rate of 92.0% at 5 years and 84.0% at 10 years; patients with stage II tumors had a survival rate of 82.0% at 5 years and 75.0% at 10 years. The percentage of patients with local recurrences was 13.0% for all patients (10.8% for stage I and 16.1% for stage II patients). The percentage of patients with lymph node recurrences was 1.5% for all patients (1.3% for stage I and 1.9% for stage II patients). The percentage of patients with distant metastases was 11.2% for all patients (7.8% for stage I and 16.1% for stage II patients). Locoregional control rates compared favorably with those in the literature. Breast preservation rates at 5 years were 85.0% for stage I and 80.9% for stage II patients. Cosmetic results were judged good by physicians in 80% of patients and by 90% of the patients themselves. Complication rates were very low.

Endometrial carcinoma: a comparative analysis of the therapeutic results and causes of failure after treatment by radiation combined with surgery or radiation therapy alone.

At the present time endometrial carcinoma is considered to be among the most frequent of gynecological tumors and its incidence is now reaching that of cervix carcinoma. In this paper, we present the results of two series of treatment for endometrial carcinoma, one using the combination of surgery and radiation, the second one using radiation treatment alone. Indeed, due to our recruitment criteria between 1968 and 1978 at the Montpellier Cancer Institute, the proportion of patients treated exclusively by physical agents was more or less equal to those receiving combined treatment. In many cases, either because of the poor condition of the patient, or due to local involvement, irradiation alone was used. The report of the results explain the therapeutic failures and show by means of two sequential series how techniques have been developed. Previously treated patients were excluded (44 cases).

Tumorectomy and radiotherapy in early breast cancer: a report on 392 patients.

This study includes 392 patients (231 Stage I and 161 Stage II) treated by tumorectomy followed by radiotherapy. The overall actuarial survival for all the patients is 86.5% at 5 years and 78% at 10 years. The 5-year NED survival is 70.2%. The survival rates are depending on the loco-regional extension: Stage I: 92% survival at 5 years and 84% at 10 years; Stage II: 82% survival at 5 years and 75% at 10 years. The percentage of local recurrences were 13% for all stages (10.6% for Stage I, 16% for Stage II), of lymph node recurrences: 1.5% for all stages, 1.3% for Stage I, 2% for Stage II, of distant metastases: 11.2% for all stages, 8% for Stage I and 16% for Stage II. The loco-regional control rates were analyzed according to the TNM classification and discussed and compared to several literature data. The breast preservation rates were at 5 years 85% for Stage I and 80.9% for Stage II. Cosmetic results are judged as good in 80% by doctors and in 90% by patients themselves with very low complication rates.

Radiotherapy alone in carcinoma of the intact uterine cervix according to G. H. Fletcher guidelines: a French cooperative study of 1383 cases.

A French Cooperative study of 1383 cases with invasive carcinoma of the intact uterine cervix treated with radiation therapy alone, using the guidelines provided by G. H. Fletcher led to the following conclusions: The techniques of treatment were easily reproducible in 9 French centers, working in a prospective cooperative study; Results similar to those of the original study were achieved in Stages I and IIA (MDAH substaging) with a locoregional failure rate of 7%; In Stage IIB, the locoregional failure rate of 16% is also comparable in both studies; Locoregional failures in Stage III are slightly lower than those reported in Houston, probably reflecting differences in patient's prognostic factors in France and Texas; The 5-year survival rate obtained in advanced Stages (UICC FIGO staging) are among the highest in the literature (76% in Stage IIb, 62% in Stage IIIa and 50% in Stage IIIb); The rate of severe complications remains acceptable and decreased throughout the study thanks to a better use of computer dosimetry.

Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group.

From November 1977 to July 1981, 441 patients with cervical carcinoma were randomized between pelvic irradiation and pelvic and para-aortic irradiation. Included were patients with stage I and IIB with proximal vaginal and/or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery, and stage IIB with distal vaginal and/or parametrial involvement and III regardless of pelvic node status on lymphangiogram. Patients with clinically or surgically involved para-aortic nodes were not included. The external beam dose to the para-aortic area was fixed at 45 Gy. There was no statistically significant difference between the two treatment arms in terms of local control, overall distant metastases and survival with no evidence of disease (NED), although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). The 4-year NED survival rate was 51%. The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value, but patients with a high probability of local control can benefit from extended field irradiation, despite an increase in severe digestive complications.

Endometrial cancer: a comparative analysis of the therapeutic results and causes of failure after treatment by radiation combined with surgery or radiation therapy alone.

The present study involved 215 endometrial carcinoma patients. Ninety-nine were treated by combined irradiation and surgery (preoperative external irradiation and intracavitary insertion followed by total hysterectomy and lymphadenectomy). Radiotherapy alone was used with 116 patients i.e. whole pelvis external irradiation and Heyman radium packing (40 patients) or afterloading techniques with Fletcher-Suit-Delclos applicators and cesium (76-patients). The 5-year NED survival rate was 78.7% in the combined therapy group and 44% in the exclusive radiotherapy group. The locoregional recurrence rates were 10% in the combined group and 28% in the exclusive radiotherapy group. These results are discussed in relation to data in the literature and to biases introduced due to patient selection in this nonrandomized study. Five-year survival rates, locoregional recurrence rates and sites of failures are analyzed according to the different treatments. Modifications of the external irradiation and intracavitary techniques allowed us to obtain better results and fewer complications.

A quantified approach to the analysis and prevention of urinary complications in radiotherapeutic treatment of cancer of the cervix.

This paper is the report of a dosimetric study of 79 urinary complications after radical radiation treatment (1975-1979) of 624 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit-Delclos applicator). Dosimetric-computerized studies were expressed as the maximum bladder dose on the trigone, as proposed by the I.C.R.U. Bladder doses were actually studied as a function of intracavitary irradiation and intracavitary + external irradiation. The results show a significant difference in patients with and without complications based on the dose reaching the bladder. The relative contribution of external therapy and intracavitary irradiation and their value can serve as one of the primary indicators for predicting complications. These values should be determined before placement of intracavitary sources. We found that the dose to the critical organs cannot be defined as a single number. These results argue in favor of adapting individual patient therapy based on rectal and bladder dosimetry and may be adjustable to all treatment modalities.

[Long-term results of the treatment with physical agents exclusively in a series of cancers of the uterine cervix. Cooperative study of 1,383 cases]. / Résultats à long terme du traitement par les agents physiques exclusifs d'une série de cancers du col utérin. Etude coopérative de 1,383 cas.

The authors present a study of 1,383 cases of invasive carcinoma of the cervix treated exclusively by radiotherapy between 1970 and 1981. Combination external radiotherapy followed by intra-cavitary applications was carried out. The study was carried out in 9 different radiotherapy centres in France using the same protocol and the same recording systems. The therapeutic results which have been recorded at every stage are among the best obtained until now, with 90% success for stage I after 5 years, 80% success for stage II, 52% for stage III growths. Only 2.1% failures occurred in the cervico-vaginal region. Pelvic recurrences were 7% in stage I and IIA, 14% in stage IIB and 24% in stage III. These recurrence rates are lower than have generally been recorded. Complication rates are also low and became less as the study continued, thanks to better use of dose distribution in individual cases which took note of doses received by neighbouring organs. The prognostic value of lymphography was analysed.

Cancer of the piriform sinus: treatment by radiation therapy alone and with surgery.

To ascertain the optimal treatment for carcinoma of the piriform sinus, the authors determined survival rates and local and regional tumor growth for two groups of patients: those treated by radiation therapy alone (n = 209) and those treated by radiation therapy combined with surgery (n = 154). The two groups were similar with respect to the characteristics of primary tumor stage and degree of nodal involvement. The overall 3-year and 5-year actuarial survival rates were 19.2% and 15.5%, respectively. For 5-year actuarial survival, there was no significant difference between patients with T1 and T2 tumors, but there was a significant difference between patients with T1 + T2 tumors versus those with T3 tumor. There was no significant difference in 3- and 5-year survival between patients with N0 and N1 nodal involvement and those with N1 and N2 involvement, but there was a significant difference between patients with N0 versus those with N3 involvement. The 5-year actuarial survival rate is significantly better for patients who underwent surgery followed by radiation therapy than for those who received only radiation therapy. However, for patients with early-stage (T1 and T2) tumors, radiation therapy alone controls local tumor growth as well as the combination of surgery and radiation therapy does. For each treatment group, the causes of death and patterns of failure were studied and compared with investigations to date.