Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast cancer: Results of a prospective study.

PURPOSE: To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. MATERIAL AND METHODS: This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. RESULTS: Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18-77 months). Median age was 53 years old (range: 23-68 years). The 3-years overall survival was 93% (range: 87-100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. CONCLUSIONS: Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Stereotactic body re-irradiation therapy for locally recurrent prostate cancer after external-beam radiation therapy: Initial report.

PURPOSE: Management of prostate cancer relapses after external-beam radiation therapy is still undefined. Re-irradiation schedules have been explored in different tumour sites. In this report, we present our preliminary experience of re-irradiation using stereotactic body radiotherapy for localized prostate cancer failure. MATERIAL AND METHODS: Between March 2011 and October 2014, robotic stereotactic body radiation therapy was administered to patients previously treated with external-beam radiation therapy to a median dose of 71.1Gy (range, 45-76.5Gy) and with biochemical failure corresponding to a local in-field recurrence of prostate cancer. Ten patients had recurrences after postoperative external-beam radiotherapy. Patients underwent a pelvic MRI to confirm the recurrence and a total body staging using a ((18)F)-fluorocholine PET/CT. The prescription dose consisted of five fractions of 7.25Gy to a total dose of 36.25Gy. Efficacy was evaluated based on biochemical response and toxicity was evaluated according to CTCAE v.4.0 questionnaires and International Prostate Symptom Score. RESULTS: Twenty-one patients were treated and followed for a median time of 11.7 months (mean: 13.4 months; range: 2.5-46.5 months). Median time between the first external-beam radiation therapy of prostate cancer and the first day of CyberKnife(®) treatment was 111 months (range: 38-398 months). One-year biochemical recurrence-free survival rate was 83.3%, and only one in-field progression was reported. Two patients had a biochemical failure corresponding to metastatic progression without evidence of local recurrence. Treatment was well tolerated, with only one grade 2 acute genitourinary toxicity, no grade≥2 acute gastrointestinal or late toxicities were reported. CONCLUSION: Stereotactic body re-irradiation therapy using CyberKnife(®) after failed external-beam radiation therapy showed favourable results in terms of in-field local and biochemical control. Toxicity was low and acceptable. Further prospective studies are needed to confirm these results to select patient and to evaluate the introduction of androgen-deprivation therapy.

Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer.

OBJECTIVE: To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). METHODS: Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. RESULTS: From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). CONCLUSION: The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. ADVANCES IN KNOWLEDGE: The largest series of this association.

[Acute skin toxicity in breast intensity modulated radiotherapy using field in field technique]. / Toxicité aiguë cutanée de l'irradiation mammaire avec modulation d'intensité avec technique de champ dans le champ (optimisation avec pré-segmentation).

PURPOSE: The optimization with presegmentation irradiation technique (Dosisoft™), used in treatment of breast carcinomas, facilitates the treatment delivery and improves radioprotection. The objective of our study was to evaluate the potential impact of this innovative technique on the acute skin toxicity especially on the rate of moist desquamation during irradiation of the whole breast after conservative surgery. PATIENTS AND METHODS: The scores of acute skin toxicity observed at 50 Gy in 103 patients treated with the presegmentation technique were compared to those of 101 patients with similar breast size treated with a classic 3D technique. All patients received 50 Gy/2 Gy per fraction, 5 days a week using 4 MV photon beam. The boost on the tumoural bed was realized according to conventional technique. Using the NCI-CTCAE V4, the skin toxicity was recorded every week during the medical visit. Moreover, the following factors that could induce skin toxicity have been studied: breast size, body mass index, age, prior chemotherapy, concurrent administration of trastuzumab, hypertension, diabetes, smoking habits and statin uptake. RESULTS: The incidence of moist desquamation observed in all sites, has been decreased to only 9.8% in the presegmentation group versus 16.8% in the test group, the difference being not statistically significant OR=0.53 [0.23; 1.22] (P=0.13). In univariate analysis the presegmentation technique enabled a significant decrease of 4.4 Gy in mean, of the value of maximum dose (P=0.001). The other risk factors of skin toxicity are the increase of breast size (P<0.001), a high body mass index (P<0.001), hypertension (P=0.03) and concurrent administration of trastuzumab (P=0.07). In multivariate analysis, the two remaining significant factors are breast size (OR=1.004 [1.002; 1.006]) and trastuzumab administration (OR=4.95 [1.17; 20.79]). CONCLUSION: The comparison of the skin toxicity induced by the presegmentation or the reference technique shows a trend regarding the improvement of the skin tolerance when using the presegmentation technique, thus pleading in favour of its use considering its dosimetric interest and the improvement of radioprotection of the patient. The next step will consist to experiment the simultaneous boost on tumoural bed using this technique.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

[Documentation management: from theory to practice]. / La gestion documentaire: de la théorie à la pratique.

The management of the documentation is one of the key points regarding the efficacy and the performance of the quality management of health centres. It offers to all professionals the possibility to be informed on the procedures in use, leading to a pool of documents for improvement of organisations and for securing the critical steps of the patient management. In this paper, we will describe the optimal organisation of the documentation according to Haute autorité de santé (HAS) and ISO recommendations, then we will discuss in concrete terms the potential methods usable for the production of a tool well adapted to our routine practice, in order to achieve the objectives for security.

The use of MRI in planning radiotherapy for gynaecological tumours.

Parameters that significantly influence results in radiation treatment of gynaecological malignancies are mainly related to the tumour characteristics and the radiotherapy technique used. High-dose radiotherapy requires accurate localisation of the tumour volume and its relationship to surrounding normal tissues. For many years the standard technique used for irradiation of the pelvic area was the four-field box technique which offered the potential benefit of the lateral fields to shield the rectum and small bowel. However, this conventional technique was designed according to bony landmarks and offered limited information regarding the topography of the tumour and the flexion of the uterus which are influenced by the tumour burden and bladder and rectal filling. CT and MRI enable the visualisation of the cervix, uterus, vagina, iliac vessels and organs at risk, but MRI allows tumour depiction in all planes. In the early 1990s, several studies reported on the value of pelvic MRI in designing the lateral fields of the box technique. They demonstrated that conventional lateral portals would have resulted in a marginal tumour miss and incomplete coverage of the uterine fundus in more than 50% of cases, thus leading to the conclusion that if a box technique is used its design should be based on sagittal MRI. CT-based 3D planning systems are now routinely used in the vast majority of radiotherapy departments. Target volumes and organs at risk are delineated by the physician on each CT slice in order to conform the radiotherapy fields to the tumour volume. For several reasons, such as distortion and lack of electron density which is essential for dose calculation, the implementation of MRI into radiation treatment planning has its limitations. However, MRI can still be used if planning systems integrate tools for CT/MR image registration. There is little experience in the literature for gynaecological malignancies demonstrating that image fusion allows an improvement of the definition of the target and the organ at risk compared to CT alone. Only a few papers in the literature report on the use of CT/MR image registration in planning the external irradiation of gynaecological tumours. Most demonstrate feasibility, but they fail to quantify the improvement for volume definition compared to the use of CT alone. Finally, recent possibilities offered by MRI technology are promising in the area of brachytherapy planning as the full potential of individually defining and evaluating GTV and CTV based on tumour extent and anatomical structures is exploited.

Radiotherapy with high dose rate brachytherapy boost and concomitant chemotherapy for Stages IIB and III esophageal carcinoma: results of a pilot study.

PURPOSE: Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard treatment for non resectable esophageal cancer. Usual total radiation dose is 50 Gy. In order to enhance local control rate a Phase II study was initiated to evaluate the feasibility of a combined treatment with an external radiation dose of 60 Gy and three cycles of concomitant CT, using the three main active drugs (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering 10 Gy. METHODS AND MATERIALS: Fifty-three patients, 48 men and 5 women, were entered in this study. Stages were evaluated with CT scan and with endoscopic sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per fraction, one fraction per day and five fractions per week. The CT regimen was a combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2 continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day 1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was delivered one week after the end of external radiation therapy. RESULTS: Full radiation therapy dose was delivered for 94% of the patients. CT compliance, evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and 51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%, respectively. Haematologic toxicity was the most limiting factor. One patient died from treatment toxicity. Local control rate at one year was 74%. Three-year actuarial survival rate was 27%. Distant metastasis was the main cause of treatment failure. Swallowing score was good for 75% of the patients. Stage, performance status and weight loss were prognostic factors. CONCLUSION: This regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible; however, a high level of haematologic toxicity was observed with the CDDP, 5FU and MMC regimen. Despite a poor compliance with CT, treatment results are very encouraging for patients with locally advanced disease.

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

[Effect radiotherapy on postoperative staging and residual tumor cell density in rectal cancers]. / Influence de l'irradiation sur le stade postopératoire et la densité de cellules tumorales résiduelles dans les cancers du rectum.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and sterilization after preoperative radiotherapy for rectal cancer. PATIENTS AND METHODS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma underwent preoperative radiotherapy (median dose, 44 Gy; mean time before surgery, 5 weeks). Pathologic specimens were reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC) and to quantify residual tumor cell density (RTCD). RESULTS: According to the MAC, there were nine stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%) and 45 stage C1-C3 (27%) tumors. Seventeen per cent and 56% of the patients who received a dose > or = 44 Gy presented with stage 0-A and stage B1-B3 tumors, respectively, compared to 4 and 69% of those who received a dose < 44 Gy (P = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with more frequent downstaging. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells; 62 (37%) showed an intermediate RTCD and 43 (26%) a high RTCD. No predictive factor of RTCD was statistically significant. Only post-operative staging was a significant prognostic factor (P < 0.01). CONCLUSION: The favourable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Tumor differentiation and time before surgery were the other significant predictive factors of tumor downstaging. Even after preoperative radiotherapy, post-operative staging retained its prognostic value.

Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and concomitant cisplatin, 5-fluorouracil and mitomycin C.

The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day 4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival rates were 48 and 31%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade > 2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo- and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible.

[Concomitant radiochemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced carcinoma of the oropharynx. Results of a phase II trial]. / Radiothérapie et chimiothérapie concomitante par cisplatine (CDDP), 5-fluorouracile (5-FU) et mitomycine C (MMC) pour le traitement des cancers localement évolués de l'oropharynx. Résultats d'un essai de phase II.

In order to improve loco-regional control in locally advanced oropharyngeal carcinoma, a phase II trial was designed to establish the feasibility of concomitant conventional radiotherapy and three cycles of chemotherapy at day 1, 21 and 42 with cisplatin (CDDP) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 day 1 to day 4, and mitomycin C (MMC) 10 mg/m2 day 1. From March 1990 to September 1993, 27 patients (mean age: 55) were included in this study. Three patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of disease; among the 17 other patients, seven died with cancer. Loco-regional control rate was 85%. One and 2-year survival rates were respectively 48 and 31% for overall and disease-free survival; respective corrected overall survival rates were 68 and 61%. Grade 3 or 4 mucositis was 81%; enteral feeding was necessary for 63% of the patients; mean loss of weight was 5.7 kg. Grade > 2 thrombopenia occurred in 11 patients (41%), grade > 2 neutropenia in eight patients (29%) , grade > 2 anemia in four patients (15%). Febrile neutropenia or aplasia occurred in five patients (19%). Two patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 2 months after treatment with grade 4 thrombopenia and septicemia. Addition of MMC to 5-FU and CDDP might have been partly responsible of this increased toxicity. A high complete response rate has been achieved with this concomitant radio-polychemotherapy, but with a severe digestive and haematological toxicity, which did not allow to conclude to the feasibility of this therapeutic association.

Abdomino pelvic irradiation after second-look laparotomy for stage III ovarian carcinoma.

OBJECTIVE: The purpose of this retrospective analysis of 34 patients with stage III ovarian carcinoma was to review results and morbidity of whole abdominal irradiation after surgery and chemotherapy. METHODS AND MATERIALS: All of the 34 patients had reached a complete clinical remission after first cytoreductive surgery and chemotherapy. After second-look laparotomy each patient underwent whole abdominal irradiation. Except for two patients with chronic myelosuppression, the dose administered was of 22.5 Gy to the abdominal cavity with a boost of 22.5 Gy added to the pelvis. RESULTS: Three and 5-year overall survival rates were 62% and 43%, respectively. Three and 5-year disease-free survival rates were 53% and 38%. Twenty-three patients (68%) developed local relapse or local disease progression. Metastasis occurred in five cases and were always associated with an abdominal cavity recurrence. Residual disease after first cytoreductive surgery appeared as a prognostic factor in univariate analysis. Patients with unresected residuum had a 5-year survival probability of 35% versus 83% for patients without residual disease. We observed 12% grade-3 intestinal toxicities and one fatal case of radiation enteritis. CONCLUSION: Despite its curative potential, the long term benefit of whole abdominal irradiation in the multimodality treatment of advanced ovarian carcinoma must be evaluated in well designed controlled trials.

Conservative treatment feasibility with induction chemotherapy, surgery, and radiotherapy for patients with breast carcinoma larger than 3 cm.

BACKGROUND: The traditional surgical treatment for operable breast carcinoma larger than 3 cm is mastectomy. To avoid mutilating surgery, the authors administered primary chemotherapy to 158 patients with operable nonmetastatic large breast carcinoma with a TNM classification of T2 greater than 3 cm and T3 with a lymph node status of N0-N1. Conservative treatment was proposed for patients responding to the chemotherapy and whose tumor was reduced to 3 cm or less. The purpose of the study was to evaluate the feasibility and treatment results of this strategy. METHODS: The mean patient age was 50.4 years. Eighty-two patients had T2 carcinomas greater than 3 cm, and 76 had T3 carcinoma. Fifty-four tumors were classified as lymph node status N0, and 104 as N1. Mean tumor size was 5.6 cm. Patients were treated with three courses of the NVCF regimen (mitoxantrone, vindesin, cyclophosphamide, and 5-fluorouracil) or the EVCF regimen, in which mitoxantrone was replaced by epirubicin every 4 weeks, and then administered with a radiosurgical combination. RESULTS: The overall response rate to induction chemotherapy was 60.8% with 20.2% complete tumor regression. Twenty-one percent of the patients experienced grade 3 or 4 chemotherapy toxic effects, which were all acceptable and reversible. Breast-conserving treatment was feasible in 48.7% of patients (77 of 158). Forty-five patients (28.5%) were treated with a radiosurgical combination (tumorectomy plus radiation therapy), whereas 32 (20.2%) were treated with radiotherapy alone (external irradiation and brachytherapy). Other patients were treated with mastectomy. Age, tumor stage, histology, hormonal status, and hormonal receptor rate had no influence on the frequency of the observed regressions. Isolated recurrences occurred in 11 patients, 6 who were treated conservatively and 5 who were treated with mastectomy. Metastatic relapses were observed in 38 patients (14.6% in the chemotherapy responders and 38.7% in the nonresponders) (P < 0.02). Five-year actuarial survival was 73.2% and was significantly higher for responders to the induction treatment. CONCLUSION: These preliminary results suggest that primary chemotherapy and radiosurgical breast-conserving treatment is feasible and is an alternative to mastectomy for patients with large operable breast carcinoma who are responders to the induction treatment. The long term benefit of this strategy must be evaluated in well designed controlled trials.

Primary chemotherapy and radiosurgical breast-conserving treatment for patients with locally advanced operable breast cancers.

PURPOSE: The traditional surgical treatment for operable breast cancer larger than 3 cm is mastectomy. In order to avoid mutilating surgery, we administered primary chemotherapy to 80 patients with operable non metastatic large breast cancer T2 > 3 cm and T3, N0-N1. The purpose of the study was to evaluate the breast-conserving rate induced by this treatment strategy and determine if it is a safe alternative for women with locally advanced breast carcinomas that are responders to an induction chemotherapy. METHODS AND MATERIALS: The mean age was 50.1 years. Forty-three patients were T2 > 3 cm, 37 were T3. Twenty-six were N0 and 54 were N1. Mean tumor size was 5.4 cm. Patients were treated with three courses of the MVCF regimen (Mitoxantrone, Vindesin, Cyclophosphamide, and 5 Fluorouracil) every 4 weeks and then with a radiosurgical combination. RESULTS: The overall response rate to induction chemotherapy was 51% with 17.5% complete tumor regression. Twenty-one percent of the patients developed grade 3 or 4 chemotherapy toxic effects, all acceptable and reversible. Breast-conserving treatment was feasible in 42.5% (34/80). Twenty patients (25%) were treated with a radiosurgical combination (tumorectomy+radiation therapy), 14 (17.5%) with radiotherapy alone (external irradiation and brachytherapy). Age, tumor stage, histology, hormonal status, hormonal receptors rate had no influence on the frequency of the observed regressions. Isolated recurrences occurred in five patients, two conservatively treated and three treated with mastectomy. Metastatic relapses were observed in 20 patients (12% in the responders and 38.5% in the non responders to chemotherapy) (p < 0.02). Five-year actuarial survival was 73% and was significantly better for responders to the induction treatment. CONCLUSION: These results suggest that primary chemotherapy and radiosurgical breast conserving treatment is a safe alternative to mastectomy for patients with locally advanced operable breast cancer. The long-term benefit of this strategy must be evaluated in well designed controlled trials.

Disappearance of the in situ component: a criterion predictive of metastasis in breast cancer after local relapse.

Local recurrence after conservative treatment of breast cancer is associated with a significant risk for metastasis. In order to identify criteria predictive of metastasis in this subset of women, we analyzed a series of 35 patients with local relapse among 512 consecutive patients treated with tumorectomy and radiotherapy. When relapse occurred within 2 years of initial treatment, overall 2-year survival from the time of local relapse was 39.5%. When local relapse occurred more than 2 years from initial therapy, 2-year survival was 80.5% (p < 0.001). Pathological slides of both initial and recurrent tumors were reviewed and compared. In 17 patients, local relapse and initial tumor had the same morphological features, with an in-situ component either absent or present in the same proportion. Metastasis occurred in two of these patients. In contrast, 9 of 12 patients in whom the proportion of non-invasive carcinoma had decreased at the time of local recurrence developed metastasis. Overall 2-year survival from the time of relapse was significantly better in the former group of patients (93.3% versus 52.5%, p < 0.05). We concluded that early relapses have a poor prognostic significance and that disappearance of the in-situ component or increase of the invasive component at the time of relapse is a feature predictive of tumor-related death and that more intensive therapy might benefit to this subset of women.

[Adenocarcinoma of the endometrium. The role of vaginal brachytherapy in the therapeutic sequence]. / Adénocarcinomes de l'endomètre. Place de la curiethérapie vaginale dans la séquence thérapeutique.

Surgery is the traditional treatment for endometrial carcinoma stage I and II. Radiotherapy is given to improve local control rate. Vaginal vault curietherapy can reduce vaginal recurrences rate. Chronology of curietherapy (pre or post operative) is under discussion. We have retrospectively analyzed treatment results of patients treated either with pre operative curietherapy (60 Gy) and then radical hysterectomy with bilateral salpingo oophorectomy (RH-BSO) (group 1), or with RH-BSO and then vaginal curietherapy (60 Gy) (group 2). Patients with bad prognostic factors (grade 3 and deep tumor invasion into the myometrium) received pelvic external irradiation and were excluded. 121 patients were in group 1, 63 patients were in group 2. All patients received curietherapy using Cesium 137 sources (one uterine and two vaginal sources in group 1, three vaginal sources in group 2). Total dose delivered to the reference volume was 60 Gy. Doses delivered to some reference points (vagina, rectum, bladder, pelvic wall) were calculated according to the ICRU recommendations. Surgery was at least RH-BSO performed either before or after curietherapy. 82 patients in group 1 and 44 in group 2 had a pelvic lymphadenectomy. Curietherapy data were comparable in the two groups according to the dose distribution to the vagina, rectum and bladder. Reference volume was smaller in the group 2. Local failure rate was 13% in group 1 and 10% in group 2. Distant metastases rate was 12% in group 1 and 9% in group 2. Five year actuarial survival rate was not statistically different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic value of local recurrence after conservative treatment of cancers of the breast ]. / Valeur pronostique de la récidive locale après traitement conservateur des cancers du sein.

To determine the prognostic significance of local relapse after conservative treatment of an invasive carcinoma of the breast, we analysed the results obtained in a series of 512 patients. All patients had a lumpectomy with axillary dissection followed by irradiation. Adjuvant medical treatment was administered to 168 patients. The actuarial 5 years and 10 years overall survival rates were respectively 92.5% and 79.7%. Local relapses occurred in 35 patients (6.8%). The actuarial 5 and 10 years local control rates were respectively 91.2% and 83.6%. In these patients, risk of metastasis was significantly increased as compared with patients without a local relapse. Recurrence in the breast within 2 years of initial treatment several affected the risk of metastasis occurring as compared to later relapses. We conclude that the occurrence of a breast relapse after successful local conservative treatment is a bad prognostic factor, predictive of a high risk for the development of distant metastases.

Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer.

The prognostic significance of local relapse after conservative treatment of early stage breast carcinoma has been controversial. To determine the incidence and the prognostic value of a breast relapse, we analyzed the results obtained in a series of patients with pT1pN0 presentation of breast carcinoma treated conservatively without adjuvant medical treatment. From 1976 to 1986, 202 patients with invasive breast carcinoma of less than 2 cm without lymph node involvement were treated with surgery and radiation therapy. The overall survival rate was 97.2% at 5 years. Locoregional relapses occurred in 16 patients (7.9%). In these patients, the overall survival rate was significantly decreased as compared to that of patients without local relapse (87.5% versus 98.3% at 5 years, p less than 0.001). The probability of remaining metastasis-free was also significantly decreased (80.2% vs 91.3%, p less than 0.001). Most relapses (94%) appeared at or close to the primary site. Salvage local treatment was possible in 14/16 patients (87.5%). Age, menopausal status, size and site of primary tumor, histological grade, and boost technique did not influence significantly the risk of local relapse occurrence. We concluded that the occurrence of a breast relapse after a successful local conservative treatment is a pejorative prognostic factor predictive of a high risk of distant metastasis development. There is a need to individualize factors that could allow discrimination of patients with a high probability of local relapse and subsequent metastasis.

Lymphadenectomy in the management of endometrial carcinoma stage I and II. Retrospective study of 155 cases.

In our institution endometrial carcinomas Stage I and II were treated with initial uterovaginal brachytherapy 60 Gy followed by modified radical hysterectomy with pelvic lymphadenectomy. We have studied the results in order to assess the value of lymphadenectomy in the treatment strategy. Between 1976 and 1986, 155 patients were treated (107 Stage I, 48 Stage II mean age 60.2 years). Twenty-six patients also received postoperative pelvic external beam irradiation on account of lymph node involvement and/or deep tumour invasion into the myometrium. Fourteen patients (9%) had lymph node involvement. External iliac lymph nodes were involved in 78.5% of these cases. Lymph node involvement rate was higher for stage II, grade 3 tumours and when there was deep tumour invasion of the myometrium. The rate of local (pelvic) treatment failure was 12% for node-negative patients and 36% for node-positive patients and the 5-year actuarial survival rates for the two groups were 83% and 41% respectively. As a consequence of our interpretation of the findings and influenced by the high complication rate which we attribute to lymphadenectomy and the information given by other prognostic indicators, we have changed to a policy of carrying out pelvic external radiotherapy for all Stage II, grade 2 or 3 cases and those with deep myometrial invasion. Lymphadenectomy is not performed in these cases. For patients with Stage I grade 1 tumours without deep tumour invasion only external iliac node sampling is performed. If this shows tumour, external irradiation is given in addition to vaginal vault brachytherapy.