Tibor Major

Freeze-dried human serum albumin improves the adherence and proliferation of mesenchymal stem cells on mineralized human bone allografts

Mineralized scaffolds are widely used as bone grafts with the assumption that bone marrow derived cells colonize and remodel them. This process is slow and often unreliable so we aimed to improve the biocompatibility of bone grafts by pre‐seeding them with human mesenchymal stem cells from either bone marrow or dental pulp. Under standard cell culture conditions very low number of seeded cells remained on the surface of freeze‐dried human or bovine bone graft or hydroxyapatite. Coating the scaffolds with fibronectin or collagen improved seeding efficiency but the cells failed to grow on the surface until the 18th day. In contrast, human albumin was a very potent facilitator of both seeding and proliferation on allografts which was further improved by culturing in a rotating bioreactor. Electron microscopy revealed that cells do not form a monolayer but span the pores, emphasizing the importance of pore size and microstructure. Albumin coated bone chips were able to unite a rat femoral segmental defect, while uncoated ones did not. Micro‐hardness measurements confirmed that albumin coating does not influence the physical characteristics of the scaffold, so it is possible to introduce albumin coating into the manufacturing process of lyophilized bone allografts.

Treatment planning for multicatheter interstitial brachytherapy of breast cancer – from Paris system to anatomy-based inverse planning

In the last decades, treatment planning for multicatheter interstitial breast brachytherapy has evolved considerably from fluoroscopy-based 2D to anatomy-based 3D planning. To plan the right positions of the catheters, ultrasound or computed tomography (CT) imaging can be used, but the treatment plan is always based on postimplant CT images. With CT imaging, the 3D target volume can be defined more precisely and delineation of the organs at risk volumes is also possible. Consequently, parameters calculated from dose-volume histogram can be used for quantitative plan evaluation. The catheter reconstruction is also easier and faster on CT images compared to X-ray films. In high dose rate brachytherapy, using a stepping source, a number of forward dose optimization methods (manual, geometrical, on dose points, graphical) are available to shape the dose distribution to the target volume, and these influence dose homogeneities to different extent. Currently, inverse optimization algorithms offer new possibilities to improve dose distributions further considering the requirements for dose coverage, dose homogeneity, and dose to organs at risk simultaneously and automatically. In this article, the evolvement of treatment planning for interstitial breast implants is reviewed, different forward optimization methods are discussed, and dose-volume parameters used for quantitative plan evaluation are described. Finally, some questions of the inverse optimization method are investigated and initial experiences of the authors are presented.

Compromised bone healing following spacer removal in a rat femoral defect model

PURPOSE The clinical demand for bone grafting materials necessitated the development of animal models. Critical size defect model has been criticized recently, mainly for its inaccuracy. Our objective was to develop a dependable animal model that would provide compromised bone healing, and would allow the investigation of bone substitutes. METHODS In the first group a critical size defect was created in the femur of adult male Wistar rats, and a non-critical defect in the remaining animals (Groups II, III and IV). The defect was left empty in group II, while in groups III and IV a spacer was interposed into the gap. Osteoblast activity was evaluated by NanoSPECT/CT imaging system. New bone formation and assessment of a union or non-union was observed by μCT and histology. RESULTS The interposition model proved to be highly reproducible and provided a bone defect with compromised bone healing. Significant bone regeneration processes were observed four weeks after removal of the spacer. CONCLUSION Our results have shown that when early bone healing is inhibited by the physical interposition of a spacer, the regeneration process is compromised for a further 4 weeks and results in a bone defect during the time-course of the study.

Multicatheter interstitial brachytherapy versus intensity modulated external beam therapy for accelerated partial breast irradiation: A comparative treatment planning study with respect to dosimetry of organs at risk.

OBJECTIVE To dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and intensity modulated radiotherapy (IMRT) for accelerated partial breast irradiation (APBI) with special focus on dose to normal tissues and organs at risk (OAR-s). MATERIAL AND METHODS Thirty-four patients with early stage breast cancer treated with MIBT were selected for the study. For each patient an additional IMRT treatment plan was created using the same CT data and contours as used in MIBT plans. OAR-s included ipsilateral non-target and contralateral breast, lung of both sides, skin, ribs and heart for left sided lesions. The CTV was created from the outlined lumpectomy cavity with a total margin (surgical+radiation) of 20mm in six main directions. The PTV in IMRT plans was generated from CTV with an addition of isotropic 5mm margin. The prescribed dose was 30.1Gy with 7×4.3Gy fractionation for both techniques. From dose-volume histograms quality parameters including volumes receiving a given dose (e.g. V100, V90, V50) and doses to specified volumes (e.g. D0.01cm3, D0.1cm3, D1cm3) were calculated and compared. RESULTS Except for high dose, non-target breast received less dose with MIBT. V90 was 3.6% vs. 4.8% and V50 was 13.7% vs. 25.5% for MIBT and IMRT, respectively. Ipsilateral lung was spared better with MIBT. Mean lung dose was 5.1% vs. 7.1%, [Formula: see text] was 39.0% vs. 54.3% and V5 was 32.9% vs. 41.7% in favour of MIBT. For left sided lesions the heart was generally irradiated by larger doses with MIBT. Mean heart dose was 4.5% vs. 2.0% and [Formula: see text] was 18.3% vs. 19.7%, correspondingly. Volumetric maximal skin doses were similar, but regarding dose to 0.1cm3 and 1cm3 of most exposed volume MIBT provided significantly less doses (76.6% vs. 94.4% and 60.2% vs. 87.8%, respectively). Ribs received less dose with MIBT with values of 45.6% vs. 69.3% for [Formula: see text] and 1.4% vs. 4.2cm3 for V50. Dose to contralateral breast and lung was low with both techniques. No significant differences were observed in maximal doses, but dose to volumes of 0.1cm3 and 1cm3 were less with MIBT for both organs. [Formula: see text] was 3.2% vs. 6.7% for breast and 3.7% vs. 5.6% for lung with MIBT and IMRT, respectively. CONCLUSIONS The target volume can be appropriately irradiated by both techniques, but MIBT generally spares normal tissues and organs at risk better than IMRT. Except for the heart, other critical structures receive less doses with brachytherapy. To observe whether these dosimetric findings translate into clinical outcome more studies are needed with assessment of toxicity profiles.

Izominvazív hólyagrák képvezérelt sugárkezelése intravesicalisan befecskendezett lipiodolos jelöléssel. A hólyagmegtartó kezelés új lehetősége

INTRODUCTION AND AIM To implement lipiodol as a fiducial marker of the tumor bed for image-guided radiotherapy with simultaneous integrated boost technique as part of radiochemotherapy for muscle invasive bladder tumors. METHOD Since April 2016, radiochemotherapy was performed in 3 male patients with muscle invasive, transitional cell bladder carcinoma. Prior to radiochemotherapy, tumor bed resection was performed for each patient, at the same time 10 ml of lipiodol solution was injected submucosally into the resection site, thus marking the tumor bed for escalated dose irradiation. During radiochemotherapy 51 Gy (1.7 Gy/die) to the pelvis, 57 Gy (1.9 Gy/die) to the whole bladder, and 63 Gy (2.1 Gy/die) to the lipiodol-labeled tumor bed was delivered with simultaneous integrated boost technique. The accuracy of the irradiation was controlled by daily kilovoltage CT. Early radiogenic urogenital and gastrointestinal side effects were recorded according to Radiation Therapy Oncology Group side-effects grading recommendation. RESULTS Substantial perioperative side effect or toxicity were not observed during and after the injection of lipiodol. The prescribed dose was successfully delivered in all patients. Radiotherapy duration was 6 weeks. The lipiodol-labeled tumor bed was clearly visible on daily kilovoltage cone beam CT. In one patient grade II cystitis and proctitis was observed, another patient experienced only grade I cystitis. These complaints improved with symptomatic medication. In the third patient no significant side effect occurred. CONCLUSIONS The injection of lipiodol into the bladder wall is a safe technique, without any perioperative toxicity or complication. The tumor bed demarcated by lipiodol was visible both on treatment planning and kilovoltage CTs. The total treatment time was shortened by 4 days. The treatment was well tolerated, early side effects were moderate, or slight. Orv Hetil. 2017; 158(51): 2041-2047.Absztrakt: Bevezetes es celkitűzes: Lipiodollal jelolt tumoragy alapjan vegzett kepvezerelt sugarkezeles, illetve szimultan integralt boost technika bevezetese izominvaziv holyagdaganatok radiokemoterapiajaban. Modszer: Izominvaziv tranziciocellularis holyagcarcinoma miatt 2016. aprilis ota harom ferfi betegunknel vegeztunk radiokemoterapiat. A radiokemoterapia megkezdese előtt mindegyikuknel tumoragy-reszekciot vegeztunk, amely soran a daganatagyba submucosalisan 10 ml lipiodolos oldatot fecskendeztunk be, igy jelolve a tumor helyet az emelt dozisu besugarzashoz. A radiokemoterapia soran 30 frakcioban a kismedencere 51 Gy-t (napi 1,7 Gy), a teljes holyagra 57 Gy-t (napi 1,9 Gy), a lipiodollal megjelolt tumoragyra 63 Gy-t (napi 2,1 Gy) adtunk szimultan integralt boost formajaban, forgoives, intenzitasmodulalt technikaval. A besugarzas pontossagat napi kilovoltos CT-vel biztositottuk. A radiokemoterapia alatt jelentkező korai radiogen urogenitalis es gastrointestinalis mellekhatasokat a Radiation Therapy O...

ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost – GEC-ESTRO Breast Cancer Working Group practical recommendations

PURPOSE This consensus statement from the Breast Cancer Working Group of Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO) aims at generating practical guidelines for multi-catheter image-guided brachytherapy in the conservative management of breast cancer patients used for either Accelerated Partial Breast Irradiation (APBI) or for a breast boost. METHODS Recent advances in techniques of multi-catheter brachytherapy were summarized and all the relevant literature was reviewed by a panel of experts. Panel members of the GEC-ESTRO experts participated in a series of conferences, supplemented their clinical experience, were surveyed to determine their current practices and patterns, performed a literature review, and formulated recommendations for implementing APBI with multi-catheter brachytherapy, focusing on treatment planning issues, catheter insertion, dosimetry and quality assurance. This document was reviewed and approved by the full panel, the GEC-ESTRO executive board and by the ACROP (Advisory Committee on Radiation Oncology Practice). RESULTS Three-dimensional (3D) treatment planning, catheter insertion techniques, dosimetry and methods of quality assurance for APBI and boost with multi-catheter image-guided brachytherapy after breast conserving surgery are described. Detailed recommendations for daily practice including dose constraints are given. CONCLUSIONS Recent standards and guidelines for the use of APBI with different multi-catheter image-guided brachytherapy techniques have been defined. Different techniques are used to insert the catheters. Guidelines are mandatory to assure precise catheter insertion for coverage of the target volume and to guarantee high-quality dosimetry. The same rules apply for brachytherapy based boost irradiation for breast cancer after whole breast irradiation as well as for partial breast re-irradiation.

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial

BACKGROUND Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. METHODS We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). INTERPRETATION APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. FUNDING German Cancer Aid.

Breast Brachytherapy: Interstitial Breast Brachytherapy

Interstitial brachytherapy used in the management of breast cancer has enjoyed broad acceptance among many in the field. It is a complex technical procedure that requires great skill and significant experience to be properly performed. We present a detailed and thorough discussion of the technique, evidence, and results in this chapter.

An overview of european clinical trials of APBI

In the last two decades, there has been increasing interest in Europe in treating selected patients with early-stage breast cancer with accelerated partial breast irradiation (APBI) using externalbeam irradiation (EBI) (Magee et al. 1996; Ribeiro et al. 1993), interstitial brachy therapy (BT) (Cionini et al. 1995; Clarke et al. 1994; Fentiman et al. 1991, 1996, 2004; Johansson et al. 2008; Mayer and Nemeskeri 1993; Ott et al. 2004, 2005, 2007; Polgar et al. 2002, 2004a, 2005, 2007, 2008; Poti et al. 2004; Samuel et al. 1999; Strnad et al. 2004), or intracavitary (MammoSite) BT (Niehoff et al. 2006a,b). In this chapter, we will give an overview of these European clinical trials of APBI, including their implications for optimal patient selection, target defi nition, treatment technique, and quality assurance (QA). Finally, we will discuss the development and status of the new European Multicentric Phase III APBI trial conducted by the Breast Cancer Working Group of the Groupe Europeen de Curietherapie–European Society for Therapeutic Radiology and Oncology (GEC–ESTRO). European experience with intraoperative radiotherapy for APBI is discussed elsewhere (see Chap. 12).

An Overview of European Clinical Trials of Accelerated Partial Breast Irradiation

In the last two decades there has been an increasing interest in Europe in treating selected patients with early-stage breast cancer with accelerated partial breast irradiation (APBI) using external beam irradiation (EBI) (Magee et al. 1996; Ribeiro et al. 1993), interstitial brachytherapy (BT) (Cionini et al. 1995; Clarke et al. 1994; Fentiman et al. 1991, 1996, 2004; Johansson et al. 2002; Mayer and Nemeskeri 1993; Ott et al. 2004, 2005a, 2005b; Polgar et al. 2000, 2002a, 2002b, 2004a, 2004b, 2005; Poti et al. 2004; Samuel et al.