[Treatment of inflammatory breast cancers at the Institut Gustave Roussy. Apropos of 230 cases].
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Biomedical subjects
Publications and source records attributed to D Sarrazin.
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1,271 patients with breast cancer treated at the Institut Gustave Roussy between 1967 and 1972 and with a minimum follow-up of 10 years, have been studied in order to analyse the risk factors for bilateralization. Patients with metastases at presentation (160) who have an incidence of bilateralization at two years of 20% have been excluded since the contralateral tumor is regarded as part of the metastatic process. For 1,111 patients, non-metastatic at presentation, the following factors have been studied: age, T-stage, N-stage, tumor grade, tumor growth rate (doubling tumor size in less than six months) and the presence of inflammatory signs. Of these factors, only advanced T stage, fixed axillary lymphadenopathy and the presence of inflammatory sign were associated with a significantly increased risk of bilateralization. For patients presenting with T1 tumors the incidence of bilateralization is 19% at 10 years but this is probably because relatively more of these patients lived long enough to develop a second cancer. A more detailed histopathological study was performed on 682 patients whose tumors were operable at presentation and for whom the following histological characteristics are known: type, grading (Scarff and Bloom), number of axillary nodes involved by tumor and anatomical size of the tumor. None of these characteristics was found to increase the risk of bilateralization. Comparing the two breast tumors (and excluding those with a diffuse infiltration in either breast) in 74 patients in whom the exact tumor site was known, in only 7, was the second tumor a "mirror-image" of the first. Overall, MO patients with bilateral tumors have a decreased survival compared with those with unilateral tumors. For those patients operable at presentation, the 10 year survival is 51% and 63%. The conclusions of this study are that there are two populations of patients with bilateral breast cancer: Those in whom the controlateral tumor is part of a generalized metastatic process and occurs particularly in those with a poor prognosis (metastases at presentation, inflammatory carcinomas, fixed lymphadenopathy). Those in whom there is a relatively long interval (5-10 years) between the development of the two tumors who have not any metastases. This population particularly comprises patients with T1 tumors thus for whom continuing clinical and mammographic follow-up is justified.
Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at operation, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, esophagus, blood vessels or mediastinum. Of 539 patients with differentiated thyroid cancer treated at Villejuif, France, until 1976, 97 were treated by external radiotherapy after an incomplete surgical excision. Fifteen years after irradiation, the survival rate is 57% and is approximately 40% at 25 years. The relapse-free survival is lower (39% at 15 years). In patients irradiated with an adequate dose (greater than or equal to 50 Gy) to residual neoplastic tissue after incomplete surgery, the incidence of local recurrence is low (actuarial probability of local recurrence 11% at 15 years versus 23% for patients treated by surgery alone, although the irradiated patients had larger and more extensive tumors). This demonstrates the efficacy of external-beam radiotherapy. The effects of radiotherapy on a residual tumor can be monitored by a serum thyroglobulin assay. With regard to local control of tumors, the effectiveness of radioiodine administration is clearly lower. However, since radioiodine facilitates early detection of distant metastases, a combination of external RT and radioiodine is indicated and is well-tolerated. For inoperable patients, the results of RT are limited: although complete remissions are sometimes obtained, the incidence of local recurrence is high. External RT is effective in medullary carcinoma despite the slow shrinkage of the tumor after irradiation. Assay of the calcitonin level helps to monitor the effects of the treatment during follow-up and has demonstrated in some patients the efficacy of cervical RT. In undifferentiated cancers, the results of RT are poor. Combination of RT and chemotherapy are being explored despite the disappointing preliminary results of this combination.
This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.
Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
During 1971-1980, three consecutive clinical studies on nephroblastoma were conducted by the International Society of Paediatric Oncology (SIOP). Besides several questions on different postoperative treatment modalities, the emphasis of these trials was to determine the role of preoperative therapy. In SIOP-1 (1971-1974) we compared preoperative radiotherapy to immediate surgery. There is no difference in survival or recurrence-free survival between both groups. Tumour ruptures, however, did occur significantly less in the pretreated group, and the recurrence-free survival is clearly lower in patients with intraoperative tumour rupture. These results were confirmed by SIOP-2, a non-randomised study conducted between 1974 and 1976. The question tackled by SIOP-5 (1977-1980) was whether preoperative chemotherapy could be a substitute for preoperative radiotherapy. The two preoperative therapies produced equally satisfactory results in terms of recurrence-free survival and 4-year survival rates, and the reduction in the number of operative ruptures. In addition, it was shown that with preoperative chemotherapy about 45% of an unselected population of patients with Wilms' tumour can be treated and cured without any irradiation and its well-known sequelae. The actual need for radiotherapy in stage II tumours with negative lymph node involvement (about 30% of the patients after pretreatment) is under investigation in SIOP-6. Cytohistological grading is equally possible after chemotherapy, and also without pretreatment. If antitumour treatment is begun before histopathological diagnosis, then the risk of overtreating patients with benign conditions, or of administering an inappropriate treatment to patients with malignant tumours of other types, is about 6%.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast sarcoma are rare, representing 1% of all malignant breast tumours. This is a retrospective study of 25 patients with a breast sarcoma, treated at Institut Gustave Roussy from 1954 to 1981. Thirty six per cent of these arose in a cystosarcoma phyllodes. A variety of histologies were found, the main one being malignant fibrohistiocytoma (44%). Nodal involvement was rare (4%) and, as in other sarcoma, hematogenous spread of metastases was more usual. Local recurrence occurred in 44% of cases and distant metastases (usually pulmonary) in 24%. The 3 year disease-free survival was 60% and the major prognostic factor was the mitotic index. Surgery is the treatment of choice of these tumours, supplemented by local irradiation in those cases where only a tumorectomy has been performed. The role of adjuvant chemotherapy remains undefined.
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Treatment of medulloblastoma in children with head and spinal irradiation causes growth hormone deficiency and growth retardation. The present study deals with 45 patients presenting a follow-up time superior to 4 years; some of them having reached their final height. The mean final height is 3 standard deviations below normal mean. Growth retardation which occurred in 42 of 45 children, appears to be due to two major factors: 1) GH deficiency in 42 cases as assessed by the arginine insulin tolerance test. 2) Spinal lesions due to irradiation, causing early growth retardation and a reduced trunk length in most of these children. The response to hGH treatment (10 mg/kg/yr) was not sufficient in this group of patients.
Between 1978 and 1981, 21 children were treated at IGR for a poorly differentiated carcinoma of the nasopharynx. In hopes of diminishing the radiation doses and the incidence of metastases, the treatment began by either single agent or combination chemotherapy. The total dose of irradiation could be reduced to 50 Gy in 17 patients. The short term results are available for 18 cases. There were 2 isolated local recurrences, 2 isolated nodal recurrences and 1 combined local and nodal recurrence. In march 1983 the overall results revealed the following: of 21 patients initially treated, 10 are alive without local-regional recurrence (but 1 with metastases); 2 are dead metastases; 9 are lost to follow up with metastases.
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From April, 1978 to December, 1982, 87 cases of Ewing's sarcoma were registered in 12 centres of paediatric oncology in France. The results of a therapeutic protocol consisting of intensive chemotherapy (vincristine, cyclophosphamide and actinomycin with or without adriamycin) prior to tumoral irradiation, followed by maintenance chemotherapy are reported after 3 years' follow-up from the beginning of treatment. In localized sarcomas, complete remission (66/70) persisted without relapse or metastasis in 54% of the cases (78% in sarcomas of long bones, and 37% in sarcomas of short bones). In non-metastatic sarcomas of the ribs, the first remission persisted in 7/14 patients (50%). All these patients had been initially treated with chemotherapy, radiotherapy and surgical excision. These preliminary results emphasize the value of co-operative therapeutic trials in a rare tumour, demonstrate the effectiveness of the initial chemotherapy used against Ewing's sarcoma and are in favour of a combined treatment, including systematic excision, for Ewing's sarcomas affecting the ribs.
A clinical trial was conducted at the Institut Gustave Roussy between October 1972 and December 1980 to compare mastectomy with local excision plus Cobalt-irradiation, in patients with breast cancer tumors of 20 mm in diameter or less at macroscopic examination. Low-axillary dissection and extemporaneous histologic examination were carried out for all patients. If one or more positive nodes were found, complete axillary dissection was performed. The study included 179 patients. No significant difference was detected in either overall or relapse-free survival between the two groups, although the conservatively treated group showed slightly better results. The results of conservative treatment were esthetically satisfactory in 92% of the cases. The trial included a second randomization for the patients with positive axillary nodes to assess the value of nodal area irradiation; 72 patients were studied in this part of the trial. No significant differences were found between the two groups after adjustment for the number of positive axillary nodes, although the no-nodal irradiation group showed better results and less complications than the nodal irradiation group.
The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.
The relationship between the size of the primary tumour upon initial treatment and the incidence of distant metastasis during the course of the disease was investigated using data from 2648 breast cancers treated at the Institut Gustave Roussy between 1954 and 1972. This analysis suggests the existence for each tumour of a critical volume (threshold) at which the first remote metastasis is initiated. The correlation between the size of the primary tumour and the probability of metastatic dissemination was assessed as well as the influence on this correlation of two prognostic indicators: histological grade and number of involved lymph nodes. It was found that the threshold volume is strongly correlated with the number of involved lymph nodes and the histological grading.
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