Eligibility criteria according to EAU/ESTRO/SIOG guidelines for exclusive iodine-125 brachytherapy for intermediate-risk prostate adenocarcinoma patients: impact on relapse-free survival.

PURPOSE: Iodine-125 (125I) brachytherapy (BT) alone for intermediate-risk (IR) prostate adenocarcinoma (PCA) is controversial. The purpose of the study was to investigate potential predictive factors in selected IR-PCA patients treated with BT. MATERIAL AND METHODS: Among 547 patients treated with 125I BT between 2003 and 2013, 149 IR-PCA cases were selected according to NCCN classification after an additional exclusion of patients with prostate specific antigen (PSA) > 15 ng/ml and ISUP group 3. A relapse was defined as a biochemical failure, using ASTRO Phoenix definition, or a relapse identified on imaging. Survival curves were estimated with Kaplan-Meier method. Potential prognostic variables including EAU/ESTRO/SIOG guidelines eligibility criteria were analyzed using univariate and Cox's proportional hazards regression analysis. RESULTS: Of the 149 IR patients, 112 were classified as favorable, with 69 cases eligible to BT according to EAU/ESTRO/SIOG guidelines, and 37 patients were identified as unfavorable as per NCCN. Androgen deprivation therapy (ADT) was applied in 6 patients only. Percentage of positive biopsy cores were ≤ 33% and ≥ 50% for 119 and 11 patients, respectively. With a median follow-up of 8.5 years, 30 patients experienced a relapse. 10-year overall survival, progression-free survival (PFS), and relapse-free survival (RFS) were 84% (95% CI: 75-90%), 66% (95% CI: 56-75%), and 77% (95% CI: 67-84%), respectively. Failure to meet EAU/ESTRO/SIOG criteria was significantly associated with a lower RFS (p = 0.0267, HR = 2.37 [95% CI: 1.10-5.08%]). CONCLUSIONS: Brachytherapy is an effective treatment for selected IR-PCA cases. Patients who were not eligible according to EAU/ESTRO/SIOG guidelines demonstrated a lower RFS.

Impact of adjuvant hormonotherapy on radiation-induced breast fibrosis according to the individual radiosensitivity: results of a multicenter prospective French trial.

BACKGROUND: To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). RESULTS: HT- and RILAhigh were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILAlow and HT+ than in patients with RILAhigh and HT- (75.8% and 100%, respectively; p = 0.004, hazard ratio 5.84 [95% confidence interval (CI) 1.8-19.1]). Conversely, BFFS at 36 months was comparable in patients with RILAhigh and HT+ and in patients with RILAlow and HT- (89.8% and 93.5%, respectively; p = 0.39, hazard ratio 1.7 [95% CI 0.51-5.65]), showing that these two parameters influenced independently the occurrence of severe breast fibrosis. BFFS rate was not affected by the HT type (tamoxifen or aromatase inhibitor) and timing (concomitant or sequential with radiotherapy). CONCLUSIONS: HT and RILA score independently influenced BFFS rate at 36 months. Patients with RILAhigh and HT- presented an excellent BFFS at 36 months (100%). MATERIALS AND METHODS: Breast Fibrosis-Free Survival (BFFS) rate was assessed relative to RILA categories and to adjuvant HT use (HT+ and HT-, respectively) in a prospective multicentre study (NCT00893035) which enrolled 502 breast cancer patients (456 evaluable patients). Breast fibrosis was recorded according to CTCAE v3.0 grading scale; RILA score was defined according to two categories (<12%: RILAlow; ≥12%: RILAhigh).

Treatment patterns and survival in an exhaustive French cohort of pazopanib-eligible patients with metastatic soft tissue sarcoma (STS).

BACKGROUND: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07. METHODS: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed. RESULTS: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes. All patients received treatment with systemic therapy being most common (74%, n = 107), followed by radiotherapy (30%, n = 44) and surgery (23%, n = 33). Doxorubicin, alone or in combination, was the most common first line systemic therapy (65%, n = 46). Drugs without license in sarcoma were used in 38-83% of treatments depending on treatment line. 24% of frontline patients demonstrated an objective response, decreasing to 11% objective responses in second line but no responses were documented beyond second line, with median PFS declining with each additional line. Median PFS also declined in patients receiving surgery compared to those receiving no surgery (8-15 m vs 5 m). Median OS from metastatic diagnosis for patients receiving systemic therapy was double that of patients without systemic treatment (24 m vs 12 m, p = 0.007). CONCLUSIONS: Outcomes in this population were poor and declined with successive treatment. However, results suggest that further anticancer therapies in recurrent sarcoma might be beneficial.

Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial.

BACKGROUND: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial. METHODS: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here. FINDINGS: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥ 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ≥ 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ≥ 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥ 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade ≥ 2 bf + was equal to 91% for RILA ≥ 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade ≥ 2 bf + was estimated at 14%. A significant decrease in the risk of grade ≥ 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA ≥ 12% (sHR = 0.45, p = 0.002). INTERPRETATION: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology. FUNDING: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".

Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence.

PURPOSE: To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses. MATERIALS AND METHODS: Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml. RESULTS: 198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001). CONCLUSION: High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.

Exclusive brachytherapy for T1 and T2 squamous cell carcinomas of the velotonsillar area: results in 44 patients.

PURPOSE: To evaluate the role of interstitial brachytherapy as an exclusive radiotherapy modality for primary T1-T2 squamous cell carcinomas (SCC) of the velotonsillar area. METHODS AND MATERIALS: Between 1992 and 2000, 44 patients with T1-T2 SCC of the tonsil (n = 36) and soft palate (n = 8) were treated to the primary with brachytherapy alone (37 patients) or after a limited resection (7 patients). Eight patients had prior external beam radiation therapy (EBRT) for previous head-and-neck carcinoma. Nineteen patients had initial neck dissection. The mean brachytherapy dose was 58.7 Gy, and the mean reference dose rate and Ir-192 linear activity were 58.2 cGy/h and 1.51 mCi/cm respectively. RESULTS: With a 75-month median follow-up, 1 patient recurred locally. Isolated nodal relapses occurred in 4 patients, none of whom had initial neck dissection, and salvage therapy was successful in 2. Five-year overall and progression-free survival rates were 76% and 68%, respectively. Full-course radiation therapy was possible in 7 of 12 patients who developed a second primary head-and-neck carcinoma. Late toxicity was limited to 6 mild soft-tissue necroses, and was significantly associated with previous surgery to the primary and high linear activity. CONCLUSIONS: Exclusive brachytherapy for T1-T2 velotonsillar carcinomas is safe and effective, and permits definitive reirradiation for a second head-and-neck cancer. Initial neck dissection should be performed for optimal selection for exclusive brachytherapy.

Nonrigid registration method to assess reproducibility of breath-holding with ABC in lung cancer.

PURPOSE: To study the interfraction reproducibility of breath-holding using active breath control (ABC), and to develop computerized tools to evaluate three-dimensional (3D) intrathoracic motion in each patient. METHODS AND MATERIALS: Since June 2002, 11 patients with non-small-cell lung cancer enrolled in a Phase II trial have undergone four CT scans: one during free-breathing (reference) and three using ABC. Patients left the room between breath-hold scans. The patient's breath was held at the same predefined phase of the breathing cycle (about 70% of the vital capacity) using the ABC device, then patients received 3D-conformal radiotherapy. Automated computerized tools for breath-hold CT scans were developed to analyze lung and tumor interfraction residual motions with 3D nonrigid registration. RESULTS: All patients but one were safely treated with ABC for 7 weeks. For 6 patients, the lung volume differences were <5%. The mean 3D displacement inside the lungs was between 2.3 mm (SD 1.4) and 4 mm (SD 3.3), and the gross tumor volume residual motion was 0.9 mm (SD 0.4) to 5.9 mm (SD 0.7). The residual motion was slightly greater in the inferior part of the lung than the superior. For 2 patients, we detected volume changes >300 cm(3) and displacements >10 mm, probably owing to atelectasia and emphysema. One patient was excluded, and two others had incomplete data sets. CONCLUSION: Breath-holding with ABC was effective in 6 patients, and discrepancies were clinically accountable in 2. The proposed 3D nonrigid registration method allows for personalized evaluation of breath-holding reproducibility with ABC. It will be used to adapt the patient-specific internal margins.

Patient setup error measurement using 3D intensity-based image registration techniques.

PURPOSE: Conformal radiotherapy requires accurate patient positioning with reference to the initial three-dimensional (3D) CT image. Patient setup is controlled by comparison with portal images acquired immediately before patient treatment. Several automatic methods have been proposed, generally based on segmentation procedures. However, portal images are of very low contrast, leading to segmentation inaccuracies. In this study, we propose an intensity-based (with no segmentation), fully automatic, 3D method, associating two portal images and a 3D CT scan to estimate patient setup. MATERIALS AND METHODS: Images of an anthropomorphic phantom were used. A CT scan of the pelvic area was first acquired, then the phantom was installed in seven positions. The process is a 3D optimization of a similarity measure in the space of rigid transformations. To avoid time-consuming digitally reconstructed radiograph generation at each iteration, we used two-dimensional transformations and two sets of specific and pregenerated digitally reconstructed radiographs. We also propose a technique for computing intensity-based similarity measures between several couples of images. A correlation coefficient, chi-square, mutual information, and correlation ratio were used. RESULTS: The best results were obtained with the correlation ratio. The median root mean square error was 2.0 mm for the seven positions tested and was, respectively, 3.6, 4.4, and 5.1 for correlation coefficient, chi-square, and mutual information. CONCLUSIONS: Full 3D analysis of setup errors is feasible without any segmentation step. It is fast and accurate and could therefore be used before each treatment session. The method presents three main advantages for clinical implementation-it is fully automatic, applicable to all tumor sites, and requires no additional device.

[Bladder cancer chemotherapy practice study]. / Etude de pratique de la chimiothérapie dans le cancer de vessie.

OBJECTIVE: To study chemotherapy practice in invasive bladder cancer in a cancer centre (Centre Léon Bérard). MATERIAL AND METHODS: This retrospective study concerned all patients treated by chemotherapy between 1994 and 2000, either in the adjuvant setting (38) or for metastatic disease (66). RESULTS: Twenty four of the 38 patients receiving adjuvant chemotherapy were treated with MVAC, 21% developed febrile neutropenia and 60% relapsed. The median recurrence-free survival was 12 months. In patients treated for metastatic disease, the objective response rate was 36% and the median survival with advanced disease after chemotherapy was 10 months. These results are in line with those reported in large-scale randomized trials. The toxicity of chemotherapy was also fairly high (21% of febrile neutropenia). CONCLUSION: Prospective studies help to optimize chemotherapy protocols, but practice studies show the limited results and the high toxicity. The benefit/risk ratio must be carefully considered.

Role of brachytherapy in treatment of epidermoid carcinomas of the vallecula after conservative supraglottic laryngectomy followed by irradiation.

PURPOSE: To evaluate survival and functional results of the treatment of carcinomas of the vallecula using surgery, irradiation, and interstitial brachytherapy. METHODS AND MATERIALS: Between 1990 and 1998, 36 patients with squamous cell carcinoma of the vallecula were treated with horizontal supraglottic functional laryngectomy, external beam radiotherapy (median dose 54 Gy), and additional interstitial brachytherapy (median dose 16 Gy). Results were compared with a previous series of 22 patients treated without brachytherapy. RESULTS: The median follow-up was 44 months. The 5-year actuarial overall survival rate was 61.3%. The 5-year specific survival rate was 86%, with 2 local failures (local control rate 94.4%) and 4 isolated distant metastases. Ten patients developed a second primary. The overall survival was 34% for 22 patients previously treated without brachytherapy. Severe toxicities occurred in 9 patients: death (related to larynx edema or inhalation, n = 1), soft tissue necrosis (n = 1), aspiration pneumonia (n = 1), mandibular necrosis (n = 2), pharyngocutaneous fistula (n = 2), and laryngeal edema (n = 2). All the patients fed orally with no definitive gastrostomy or tracheotomy. CONCLUSION: Additional brachytherapy for vallecula carcinoma seems to improve locoregional control and overall survival dramatically. Functional results were also excellent. To our knowledge, this original therapeutic schedule has never been previously described.