Search

Purpose or Objective To limit hospital visits and transportation of the patients with early breast cancer (BC) especially during the covid-19 pandemic, we aimed to implement a workflow of treatment to prepare and deliver adjuvant breast radiotherapy (RT) within 1 week. Materials and Methods Based on the Fast Forward RT schedule of 5 fractions of 5.2 Gy over 5 days for adjuvant BC, we designed a workflow to perform BC RT over 1 week from the first RT consultation to the end of treatment (figure 1). Patients were seen in consultation on Monday morning. The planning CT was carried out immediately after the consultation. A deep inspiration breath-hold technique was systematically offered to all patients. Automatic delineation using an artificial Intelligence (AI) based model with ART-PlanTM software was first corrected by a junior radiation oncologist (RO) then, independently by a senior RO. As 3D conformal RT failed to achieve dose constraints of the fast forward trial in many cases (due to breast hotspots), we developed a restricted IMRT (rIMRT) technique based on 2 tangential beams (internal and external) using inverse planning restricted optimization parameters to improve the dose homogeneity. Treatment planning was semi-automated by scripting the creation and optimization steps of rIMRT plans. After validation of the reliability of rIMRT treatment delivery by patient-specific quality assurance (PSQA) with gamma index evaluation on 20 patients, we decided to abandon systematic PSQAs. In-vivo dosimetry was validated by end-to-end controls and performed for each patient during the first fraction on Monday afternoon. Daily repositioning was controlled by portal images of the largest segment of each beam. Structured baseline, end of treatment and follow up evaluation forms were used to prospectively collect toxicities and oncological outcomes at each consultation. Patient agreement for data collection and analysis was prospectively obtained. $Φg Results From February 2021 to March 2021, the 1-week breast procedure was proposed to up to 3 patients/week, >65 years, in complete resection after conservative surgery, with pT1-T3 N0 BC, without tumor bed boost or regional lymph nodes irradiation. Six out of seven patients (85.7%) accepted the 1-week breast procedure. All procedures were successfully conducted over 5 days with complete patient and RT team satisfaction. A followup of acute toxicities by online consultation on day 10, structured evaluation forms and management decision trees has been implemented for these patients. No grade >2 acute toxicities (CTACE V4.0) have been reported so far. Conclusion The successful implementation of this comprehensive 1-week breast workflow with AI based delineation and semi-automated rIMRT without PSQA demonstrates the practical feasibility of the whole procedure over 5 days reducing drastically the coming-and-going to the hospital and the overall RT management time per patient. Our work opens the way for further development of comprehensive compact workflows in various settings.

Background and purpose The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab). Material and methods In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The correlations between biomarker expressions and clinicopathological characteristics and treatment outcomes were analyzed. Results We found a significant correlation of MVD with UICC stage (p = 0.02) and T classification (p = 0.05), of CA-IX with UICC stage (p = 0.03) and N classification (p = 0.04) and a significant inverse correlation of MVD with CA-IX expression (r = −0.22, p = 0.03). Multivariate analysis showed that low MVD combined with high CA IX-expression was a significant independent prognostic factor for worse loco-regional control (HR = 2.6, 95%CI 1.1–5.0, p = 0.02) in the whole population but not in the p16+ subgroup. Patients treated with CRT had a better LRC than those with BRT independent of MVD or CA-IX expression. Conclusions The combination of MVD and CA-IX expression might give additional prognostic information in HNSCC patients with known HPV status.

Objective No data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters. Materials and methods Treatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42 Gy were delivered, to a total dose of 60 Gy. Results 32 patients were treated, median age 2.6 years (10 months–12 years). Median duration of each pulse was 8.5 min (3.8–17.4 min). The minimal dose in the most irradiated 1 cm3 of rectum was 44.7 Gyα/β=3 (range: 4.1–77.3 Gyα/β=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25 months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4 months (15 days–75 months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less. Conclusion PDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.

Objective To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. Materials/methods We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6–8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/− para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. Results 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity ( p =0.02). Conclusions A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

International audience; Background and purpose The dose effect-effect relationship for cardiac diseases following radiotherapy suffers from uncertainties. Three dimensional coronary artery (CA) dose calculation after mediastinal Hodgkin lymphoma radiotherapy was performed, using the patient's coronary CT angiography (CCTA), and the relationship between the coronary arteries’ radiation doses and the risk of stenosis was estimated. Materials and methods Radiotherapy simulation CT scans and CCTAs of patients treated for a mediastinal Hodgkin lymphoma were used to merge thoracic and detailed cardiovascular anatomies. Radiation treatment parameters were used to estimate CA radiation doses. Twenty-one patients without coronary stenosis (controls) were matched with twelve patients with stenosis (cases). CA segments were considered as sub-volumes of interest. Radiation doses to stenotic segments were compared with those received by normal segments (from cases and controls) using a logistic regression. Results In eleven cases out of twelve, the highest of the coronary dose distribution was on a damaged segment. Logistic regression with CA segments yielded an odds ratio associated with the risk of coronary stenosis of 1.049 per additional gray with the CA segment median dose (95% confidence interval, 1.004–1.095; p-value

Purpose Radiotherapy (RT) is used frequently in patients with melanoma, but results are suboptimal because the disease is often radioresistant. This may be due to constitutive activation of MAPK pathway signalling through mutations involving RAS/RAF. Thus, we studied whether trametinib, a potent and selective allosteric inhibitor of MEK1/2 could improve the efficacy of RT. Methods and materials Clonogenic survival assays were performed in human BRAF-mutant (A375), NRAS-mutant (D04, WM1631), KRAS-mutant (WM1791c) and wild-type (PMWK) melanoma cell lines. The effects of trametinib with and without radiation on protein levels of MEK effectors were measured by immunoblot analyses. Cell cycle effects, DNA damage repair, mitotic catastrophe and senescence were measured using flow cytometry, γH2Ax staining, nuclear fragmentation and β-galactosidase staining, respectively. Additionally, athymic mice with D04 flank tumours were treated with fractionated RT after gavage with trametinib and monitored for tumour growth. Results All cell lines, except PMWK, exhibited enhanced cytotoxicity when RT was combined with trametinib compared to either agent alone. Sensitiser enhancement ratios were 1.70, 1.32, 1.10, and 1.70 for A375, D04, WM1361 and WM1791c, respectively. Trametinib efficiently blocked RT-induced phosphorylation of ERK at nanomolar concentrations. Increased radiosensitivity correlated with prolonged G1 arrest and reduction in the radioresistant S phase up to 48h following RT. A larger population of senescence-activated β-galactosidase-positive cells was seen in the trametinib pretreated group, and this correlated with activation of two of the major mediators of induced senescence, p53 and pRb. Mice receiving the combination treatment (trametinib 1mg/kg and RT over 3days) showed a reduced mean tumour volume compared with mice receiving trametinib alone ( p =0.016), or RT alone ( p =0.047). No overt signs of drug toxicity were observed. Conclusion Trametinib radiosensitised RAS-/RAF-mutated melanoma cells by inducing prolonged G1 arrest and premature senescence. In this pre-clinical study we demonstrate that combining trametinib and RT is well tolerated, and reduces tumour growth in vivo .