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Abstract 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.

: PurposeTo assess local control, survival, and clinical and dosimetric prognostic factors in 25 patients with locally advanced maxillary or ethmoid sinus carcinoma treated by three-dimensional conformal radiotherapy (RT).: Methods and materialsSurgery was performed in 22 patients and was macroscopically complete in 16. Seven patients received chemotherapy (concomitant with RT in four). The following quality indexes were defined for the 95% and 90% isodoses: tumor conformity index, normal tissue conformity index, and global conformity index.: ResultsThe median radiation dose to the planned treatment volume was 63 Gy, with a minimal dose of 60 Gy, except in 2 patients whose cancer progressed during RT. The maximal doses tolerated by the structures involved in vision were respected, except for tumors that involved the optic nerve. After a median follow-up of 25 months, 14 local tumor recurrences developed. The major prognostic factors were central nervous system involvement by disease and the presence of nonresectable tumors. The radiation dose and tumor conformity index value were not significant prognostic indicators. Two patients died of acute infectious toxicity, and two developed late ipsilateral ocular toxicity.: ConclusionImproving local control remains the main challenge in RT for paranasal tumors. [Copyright &y& Elsevier]

Radiation plexitis, also known as radiation-induced brachial neuropathy is a rare toxicity following axillary, breast, cervical or thoracic radiotherapy, first described in 1966 by Stoll and Andrew. Although improvements in radiotherapy techniques have greatly reduced its risk over the past seventy years, its severe form remains a dreaded complication that is difficult to manage in patients with increased life expectancy. This article summarizes the epidemiological elements, risk factors, diagnostic methods, doses and constraints to be respected in radiotherapy and the treatment strategies of radiation plexitis., (Copyright © 2022. Published by Elsevier Masson SAS.)

Purpose: Iodine-125 ( 125 I) 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 125 I 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., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

The world has now been facing the coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since over a year. If most of clinical presentations are benign, fragile patients are at greater risk of developing severe or fatal lung disease. Many therapies have been explored with very low impact on mortality. In this context, Kirkby et Mackenzie have published in April 2020 a report reminding the anti-inflammatory properties of low-dose radiotherapy (delivering less than 1Gy) and its use in the treatment of viral and bacterial pneumopathies before antibiotics era. Large in vivo and in vitro data have demonstrated the biological rationale and anti-inflammatory activity of low-dose radiotherapy in many pathologies. Over the past year, three phase I/II clinical trials have been published, as well as one randomized controlled trial, reporting the feasibility and the clinical and biological improvement of a 0.5 to 1Gy treatment dose to the entire lung. 13 other studies, including a randomized phase III trial, are currently ongoing worldwide. These studies may provide data in the effect of low-dose radiotherapy in the treatment of SARS-CoV-2 pneumonia. This article explains biological rationale of low-dose radiotherapy, and reports already published or ongoing studies on low-dose radiotherapy for SARS-CoV-2 pneumonia., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

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 RILA high were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILA low and HT + than in patients with RILA high 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 RILA high and HT + and in patients with RILA low 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 RILA high 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%: RILA low ; ≥12%: RILA high )., Competing Interests: CONFLICTS OF INTEREST Pascal Fenoglietto and David Azria participated in the development of NovaGray. All remaining authors declared that they have no conflict of interest.

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.

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)".

Purpose: This work evaluated the interobserver variability in cone beam computed tomography (CBCT) registration for prostate cancers treated with intensity-modulated radiotherapy., Material and Methods: Twelve technologists realized 286 CBCT/CT registrations (bone registration followed by prostate to prostate registration). The registration results were compared to those obtained by two radiation oncologists (reference). Each technologist reported the shifts calculated by the software in all three axes. A statistical analysis allowed us to calculate the minimum threshold under which 95% of the observers found similar values. A variance analysis followed by the post hoc test were used to find differences in interobserver registration variability and determine whether any individual users performed registrations which differed significantly from those of the other users., Results: The registration differences compared to the reference in the three directions in terms of 95th percentile are: 2.1mm left-right, 3.5mm target-gun, 7.3mm anterior-posterior. In the posterior direction, 4% of the observers have found differences superior to 8mm, margin used in routine without the use of a daily CBCT. The variance test revealed a P-value <0.05 only for target-gun and for all observers there was no significant difference compared to the reference., Conclusion: This study confirmed the interest of a 3D tissue registration for prostate treatments. The registration study showed a good interobserver reproducibility. This showed the importance of a daily CBCT/CT registration in prostate treatment with the possibility of a planning target volume margin reduction in the three directions. An evaluation of a partial delegation of registration to technologists should be done by the radiation oncologists., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

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.

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.

Germ-cell tumors of the testis are rare tumors of the young adult. Half of them are seminoma. The majority of patients have disease limited to the testis. Radiotherapy still remains the standard treatment of these patients. Almost all patients are cured by orchidectomy and radiotherapy on the lomboaortic area extended to homolateral iliac area. The dose is 24 to 30 Gy in a standard fractionation. Different studies are ongoing to reduce the irradiation field (omission of the pelvic irradiation), to decrease irradiation dose (to 20 Gy). Other treatment options are strict surveillance and adjuvant carboplatin based chemotherapy. None of these options are standard treatments. A strict attention must be directed on controlateral germ-cell tumors and second cancers.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breathhold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. These techniques presently investigated in several medical centers worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. Physical, technical and physiological questions still remain to be answered. This paper describes the most frequently used gated techniques and the main published clinical reports on the use of respiration-gated radiotherapy in order to evaluate the impact of these 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.

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.

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.