Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

[Benefits of breathing-adapted radiation therapy for breast cancer]. / Bénéfices de la radiothérapie avec asservissement respiratoire dans le traitement du cancer du sein.

PURPOSE: The purpose of this study was to compare free-breathing radiotherapy, end-expiration gating and end-inspiration gating for left breast cancer, with respect to the target volume coverage and dose to organs at risk. PATIENTS AND METHODS: Sixteen patients underwent 3D and 4D simulation CT. For each patient, five dosimetric plans were compared: free breathing, end-inspiration gating, end-expiration gating, and two optimised plans with a 3mm reduction of the posterior field edge to create optimised end-inspiration and end-expiration plans. Dose-volume parameters, including planning target volume coverage and dose to lung, heart and left anterior descending coronary artery were analysed. RESULTS: Planning target volume coverage was adequate and similar in the five dosimetric plans (P=0.49). Significant advantage was found for end-inspiration gating in sparing the ipsilateral lung, heart and left anterior descending coronary artery compared to free-breathing 3D radiotherapy. Optimised end-inspiration was even more favourable than end-inspiration gating (P<0.05), with less dose delivered to the ipsilateral lung, heart and left anterior descending coronary artery. When compared to end-expiration gating, end-inspiration gating dosimetric outcomes were similar regarding lung and left anterior descending coronary artery doses, but the heart dose was inferior on the end-inspiration gating compared to end-expiration gating. CONCLUSION: Breathing-adapted radiation therapy allowed for dose reduction to organs at risk (left lung, heart and left anterior descending coronary artery), while keeping the same planning target volume coverage. Therefore it can be considered as an interesting option for left breast cancer radiation treatment.

[Erectile dysfunction evaluation after brachytherapy for low risk prostate adenocarcinoma: prospective study of patients with a baseline IIEF5>16]. / Évolution de la fonction érectile après curiethérapie prostatique : étude prospective chez des patients ayant un score IIEF5 initial>16.

PURPOSE: To evaluate erectile function (EF) prospectively from 1 to 2 years post-brachytherapy in patients with a baseline IIEF5 score>16. METHODS: Between 2007 and 2012, 179 patients underwent an exclusive brachytherapy for localised low risk prostate adenocarcinoma. Neo-adjuvant hormotherapy (15.6%) and post-brachytherapy intake phosphodiesterase inhibitors (PDE5i) were not considered as exclusion criteria. EF was evaluated via a scoring questionnaire IIEF5 before the surgical implantation, at month 12 and 24 post-operation. Only patients with an initial IIEF5 score>16 were included. RESULTS: Of the 179 patients, 102 (57%) had a baseline IIEF5>16. At 12 months, 51.1% maintained an IIEF5>16 and 24.5% had a mild to moderate erectile dysfunction (ED), so that a total of 75.6% with IIEF5≥12. About 18% of patients had used PDE5i. At 24 months, 53.2% had an IIEF5>16 and 80.6% had an IIEF5≥12. Severe ED was reported in only 14.5% of the patients. The mean IIEF5 was 16.2 with an average decline of 5 points from the initial stage. All patients who were treated with PDE5i (27%) could have sexual intercourse. EF at baseline was reported as the only predictive factor of ED in multivariate analysis, 70% of patient without ED initially, had an IIEF5>16 at 1 and 2 years. CONCLUSION: Severe ED was quite rare (14%) during the first 2 years post-brachytherapy and more than half of patients maintained an IIEF5>16. The main predictive factor was the erectile function at baseline. LEVEL OF EVIDENCE: 4.

Cervix cancer brachytherapy: high dose rate.

Cervical cancer, although less common in industrialized countries, is the fourth most common cancer affecting women worldwide and the fourth leading cause of cancer death. In developing countries, these cancers are often discovered at a later stage in the form of locally advanced tumour with a poor prognosis. Depending on the stage of the disease, treatment is mainly based on a chemoradiotherapy followed by uterovaginal brachytherapy ending by a potential remaining tumour surgery or in principle for some teams. The role of irradiation is crucial to ensure a better local control. It has been shown that the more the delivered dose is important, the better the local results are. In order to preserve the maximum of organs at risk and to allow this dose escalation, brachytherapy (intracavitary and/or interstitial) has been progressively introduced. Its evolution and its progressive improvement have led to the development of high dose rate brachytherapy, the advantages of which are especially based on the possibility of outpatient treatment while maintaining the effectiveness of other brachytherapy forms (i.e., low dose rate or pulsed dose rate). Numerous innovations have also been completed in the field of imaging, leading to a progress in treatment planning systems by switching from two-dimensional form to a three-dimensional one. Image-guided brachytherapy allows more precise target volume delineation as well as an optimized dosimetry permitting a better coverage of target volumes.

Impact of learning curve and technical changes on dosimetry in low-dose brachytherapy for prostate cancer.

PURPOSE: To assess the impact of experience and technical changes on peri- and postimplantation (1 month later) dosimetry for permanent prostate brachytherapy (PPB). PATIENTS AND METHODS: From July 2003 to May 2010, 150 prostate cancer patients underwent low-dose, loose-seed I(125) PPB as monotherapy with intraoperative planning. Patients were divided into three groups-P1 (n = 64), P2 (n = 45), P3 (n = 41)-according to the technical changes that occurred during the study period: use of an automatic stepper at the beginning of P2 and a high-frequency ultrasound probe in P3. Peri- and postimplantation dosimetric parameters (on day 30) were reported: D90 (dose received by 90% of prostate volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10 and D30 (doses received by 10% and 30% of the urethra, only during peri-implantation). RESULTS: We observed a decrease in the number of needles and seeds used over time. The mean peri-implantation D90 was 187.52 Gy without a significant difference between the three periods (p = 0.48). The postimplantation D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with no significant difference between the three periods. The peri-implantation and postimplantation D0.1 cc and R100 significantly decreased over time; on day 30: D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10(-5)) and R100 P1 = 1.06 cc vs. R100 P3 = 0.53 cc (p = 0.0008). CONCLUSION: We observed a learning curve for the implantation parameters, which led to a significant decrease in the rectal doses without having any impact on the prostate dosimetric parameters.

[How to irradiate bone metastases?]. / Radiothérapie des métastases osseuses: quel est le meilleur schéma de radiothérapie?

Radiotherapy for bone metastases represents an important part of daily practice in our departments of radiotherapy. Majority of treatments deliver either one fraction (6 to 10 Gy) or multifractions mainly using 30 Gy in ten fractions. In the past decade, several randomized trials aimed to determine the optimal scheme of radiotherapy in this setting. In the present review, the efficacy of radiotherapy on bone metastases will be evaluated using the following parameters: the partial or complete responses on pain, the reduction of antalgic intake, bone recalcification, and need for reirradiation. Other parameters must also be considered, such as the primary site, number of metastasis, performance status, overall prognosis and side effects of radiotherapy.

[Carcinosarcoma of the ovary]. / Le carcinosarcome ovarien.

Ovarian carcinosarcoma, also called malignant mixed mesodermal tumour, is a rare ovarian tumour representing less than two per cent of ovarian cancers. Carcinosarcoma is an aggressive tumour, which associates some epithelial elements (carcinoma) with a stromal component (sarcoma). This tumour can be found in the female genital tractus, mostly in the uterus. It can be found even more rarely on the ovaries. The initial stage of the disease at the diagnostic is considered as the only prognostic factor. There is no existing consensus concerning treatment. Nevertheless, surgical treatment is paramount for the survival of patients. Response rates to chemotherapy are about 20%.

[Results of surgical resection of squamous cells carcinoma of the oesophagus with or without preoperative radiochemotherapy: comparative and retrospective study]. / Résultats de la radiochimiothérapie préopératoire dans les cancers épidermoïdes de l'oesophage: étude rétrospective et comparative.

AIM OF THE STUDY: The aim of the study was to assess preoperative radio-chemotherapy for squamous cell carcinoma of the esophagus. MATERIAL AND METHODS: This study was a retrospective comparison between radio-chemotherapy followed by surgical resection (RCPO) and surgery alone. The RCPO group included patients with tumor located in the middle or lower third of the esophagus, staged T2 or T3 tumors without distant metastases by pretherapeutic assessment. These patients were matched with patients who underwent immediate surgery, who constituted the surgical group (CHIR). Both groups were matched for gender, age, tumor localization (middle or lower third), T stage, and surgical procedure. Each group included 77 men and 9 women, 50 tumors of the middle third and 36 of the lower third of the oesophagus, and 19 tumors T2 and 67 T3 ones. RESULTS: Morbidity of both groups was not significantly different. The mortality was 4% in the group CHIR and 12% in the group RCPO (P =0.07). The rate of radical resection (R0) was significantly higher in the RCPO group (74% vs. 51%; P =0.001). The overall 5-year survival rate was 38% after R0 surgery and 11% after R1 or R2 surgery (P <0.0001). After R0 surgery, the 5-year survival rate was 47% in the CHIR group and 32% in the RCPO group (P =0.06). CONCLUSION: Preoperative radiochemotherapy increases the rate of radical surgical resection without significant increase in postoperative morbidity and mortality.

[Gastroduodenal metastases: an unusual manifestation of lung cancer. Study of two cases and review ot the literature]. / Métastases gastroduodénales: un mode de révélation exceptionnel du cancer du poumon. Etude de deux cas et revue de la littérature.

INTRODUCTION: Diagnosis of gastroduodenal metastases is rare. Primary tumors are essentially melanomas and breast cancer, and exceptionally lung cancer. EXEGESIS: We report two patients who have a diagnosis of gastroduodenal metastases as initial manifestation of lung cancer. In one case, the patient died 3 weeks after the diagnosis. In the other case, chemotherapy was performed and complete response was obtained for the gastric metastasis. After a few months, node recurrence was diagnosed and the patient died 8 months after the diagnosis. CONCLUSION: We review the endoscopic and non-endoscopic literature and discuss the different histological types and therapeutic strategies concerning these unusual manifestations of lung cancer.

Tamoxifen adjuvant treatment duration in early breast cancer: initial results of a randomized study comparing short-term treatment with long-term treatment. Fédération Nationale des Centres de Lutte Contre le Cancer Breast Group.

PURPOSE: In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment. PATIENTS AND METHODS: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group. RESULTS: Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers. CONCLUSION: Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.

[Pyoderma gangrenosum and breast cancer: a new case]. / Pyoderma gangrenosum et cancer du sein: un nouveau cas.

We report here a new case of pyoderma gangrenosum (PG) associated with a breast cancer in a 39-year-old woman. We only found in literature three other reports of this rare entity which seems usually to be associated with monoclonal gammopathy, gastro-intestinal diseases such as Crohn's disease, chronic ulcerative colitis, leukemias or rheumatologic diseases. A commun hapten between of tumor and skin may explain the origin of this inflammatory lesion. In our case, PG could be a paraneoplastic syndrome.

[Fotemustine (Muphoran) in 22 patients with relapses of high-grade cerebral gliomas]. / Fotémustine (Muphoran) chez 22 patients présentant des récidives de gliomes cérébraux de haut grade.

Fotemustine is a third-generation nitrosourea characterized by a phosphoalanine carrier group grafted onto the nitrosourea radical, which gives it a high lipophilicity and a better penetration through the cell membrane. Between September 1988 and December 1997, 22 patients with inoperable or incompletely resected recurrent high-grade gliomas of the brain were treated at the University Hospital in Brest (France). Treatment consisted of three weekly infusions of fotemustine (100 mg/m2 days 1, 8 and 15). If patients responded or were stabilized, fotemustine was continued at the same dose, but every three weeks only. Four patients responded to the treatment (18%), while 6 were stabilized (32%). Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia); treatment was only interrupted in one patient for leucothrombopenia, and there was no toxic death. Medium duration of response and/or stabilisation was 6.5 months, and median survival 9.4 months in responding and/or stabilized patients, while it was only 5.0 months if tumour progressed under chemotherapy (median survival for all patients: 7.5 months). Besides, there was a difference in survival in favour of the young patients (< 50 years-median survival = 11.8 months) in comparison with patients between 50 and 60 years (median survival = 6.8 months; p = 0.0282) or elderly patients (> 60 years-median survival = 5.8 months; p = 0.0634). In our series, we did not found any difference in survival according to the initial performance status of patients before treatment. Therefore, fotemustine seems to represent an interesting well-tolerated treatment possibility in patients with inoperable recurrent malignant gliomas of the brain.

[Split-course concomitant radiochemotherapy plus surgery vs. surgery alone in squamous cell carcinoma of the esophagus. A non-randomized retrospective study of 184 patients]. / Radiochimiothérapie concomitante en split-course plus chirurgie contre chirurgie seule pour les carcinomes épidermoïdes de l'oesophage. Etude rétrospective non randomisée de 184 patients.

From April 1989 to October 1995, 184 patients with squamous cell carcinomas of the esophagus were treated either with surgery alone (112 patients) or with preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in 5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4 more courses of chemotherapy alone for good responders. Twenty-seven of these last 72 patients showed histological complete response at surgery (37.5%). There was no statistically significant difference in overall survival between the 2 groups although there were much more T1 patients (small tumors < or = 5 cm in the previous TNM classifications) and less T3 patients (evidence of spread beyond the esophagus) in the surgery alone group, and nevertheless, median survival was better in the combined treatment group (33.6 months versus 21.8 months). However, considering tumor size, there was a statistically significant difference in median survival in favor of the combined treatment group for all T2 patients (> 5 cm without evidence of spread beyond the esophagus in the previous TNM classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1 patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For the few T3 patients (evidence of spread beyond the esophagus in the previous TNM classification), there was no statistically significant difference between the 2 groups, but the survival curves seemed to show some advantage in favor of the combined treatment group for T3N1 patients. The sex of the patients and the third of the esophagus involved by the tumor did not seem to be of any influence on survival. On the other hand, patients 70-year-old and older showed a poorer survival than other patients. Finally, significantly less patients died with loco-regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%) than in the group treated by surgery alone.

Preoperative concomitant radiochemotherapy in squamous cell carcinoma of the esophagus: results of a study of 56 patients.

PURPOSE: Today the prognosis for patients with esophageal carcinoma still remains quite poor. In the last few years interesting results have been obtained by associating radio- and chemotherapy with or without surgery with this type of cancer. In this work we report the results of concomitant radio- and chemotherapy in a split-course schedule preceeding surgery for the treatment of squamous cell carcinomas of the esophagus. METHODS AND MATERIALS: Fifty-six patients with squamous cell carcinomas of the esophagus were treated between April 1989 and September 1993 in the Centre Hospitalier Universitaire in Brest, France with two courses of preoperative concomitant radiochemotherapy, separated by a 2-week interval, and followed by surgery (each course 18.5 Gy in five fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) 800 mg/m2 days 1-5 and cisplatinum 70 mg/m2 day 2). Patients who had responded well to preoperative treatment (response > 50%) received four more courses of chemotherapy alone. The two patients who were not operated and those with palliative surgery received a third course of radiochemotherapy (radiotherapy 12 Gy in five fractions, days 1-5). RESULTS: Fifty-four patients were operated on. Twenty-one showed histological complete response at surgery (37.5% of the whole group). Actuarial survival for the 56 patients was 55% at 3 years and 30% at 4 years, with a median survival of 37.4 months (40.4 months for complete responders to preoperative treatment). Toxicity of preoperative concomitant radio-chemotherapy was low (5-FU had to be stopped in one patient because of cardiac rythm disturbances and in another patient because of aplasia Grade 4 associated with infection after the first course). Postoperative mortality was 11% (six patients). CONCLUSION: This combination of preoperative radiochemotherapy followed by surgery seems to improve both response rates and survival in patients with esophageal cancer when compared with previous patients treated with surgery alone in our hospital or with results found in literature and it warrants further studies.

Delayed cerebral pseudo-tumoral radionecrosis following scalp-tumour irradiation. Case report and review of literature.

A case of delayed radionecrosis of the brain is reported, following irradiation of a scalp dermatofibrosarcoma. Signs and symptoms were those of an intracranial neoplasm and appeared 5 years after an irradiation dosage of 1890 rets. Twenty-seven similar cases were gathered from a survey of the literature. Surgical excision was the treatment of choice and led to cure or improvement in 20 cases. Analysis of doses and fractionation revealed excessive irradiation in all but one of the cases.

[Radiotherapy of primary malignant tumors of the trachea. Apropos of 31 cases]. / Radiothérapie des tumeurs primitives malignes de la trachée. A propos de 31 cas.

We report 31 cases of primary malignant tumours of the trachea, treated with radiotherapy at the Tumour Centre, Pitié-Salpêtrière, from June 1968 to January 1982. Three patients received complementary post-operative irradiation: one had an epidermoid carcinoma, operated by incomplete resection and anastomosis, and survived 12 months after irradiation with 60,00 grays in 6 weeks (local recurrence of tumour and mediastinal extension); the other two had cylindromas of the trachea with complete resection and anastomosis: the first remains alive 6 years after an irradiation of 65,00 grays over 6 weeks, the second is alive 5 years after post-operative irradiation of 60,00 grays in 6 weeks. These two latter tumours evolved slowly and local recurrence may occur after five years and sometimes longer, after local treatment. 28 other cases presenting with an epidermoid carcinoma of the trachea received radiotherapy exclusively, when a surgical cure was impossible. Irradiation was interrupted in two patients: one after a dose of 12,00 grays for sudden massive haemoptysis, the other after a dose of 22,00 grays for an oesophago-tracheal fistula. An apparent complete remission was obtained in 80% of cases, judged by a tracheo-bronchial endoscopic examination carried out in the six weeks following the treatment. Two deaths were seen from intercurrent disease: one at two months from a granulocytosis caused iatrogenically from medication and the other at five months from bilateral bronchopneumonia. One patient was alive at 9 months in apparent complete local remission, but lost to follow up.(ABSTRACT TRUNCATED AT 250 WORDS)