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Item New horizons from novel therapies in malignant pleural mesothelioma(VIA MEDICA, 2020-01-01) Sayan, Mutlay; Mamidanna, Swati; Eren, Mehmet Fuat; Daliparty, Vasudev; Mustafayev, Teuta Zoto; Nelson, Carl; Ohri, Nisha; Jabbour, Salma K.; Mert, Aslihan Guven; Atalar, BanuMalignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathogenesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several chemotherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.Item Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response(KOREAN SOC THERAPEUTIC RADIOLOGY \& ONCOLOGY, 2020-01-01) Sayan, Mutlay; Mustafayev, Teuta Zoto; Balmuk, Aykut; Mamidanna, Swati; Kefelioglu, Erva Seyma Sare; Gungor, Gorkem; Chundury, Anupama; Ohri, Nisha; Karaarslan, Ercan; Ozyar, Enis; Atalar, BanuPurpose: Approximately 10\% of patients who received brain stereotactic radiosurgery (SRS) develop symptomatic radiation necrosis (RN). We sought to determine the effectiveness of treatment options for symptomatic RN, based on patient-reported outcomes. Materials and Methods: We conducted a retrospective review of 217 patients with 414 brain metastases treated with SRS from 2009 to 2018 at our institution. Symptomatic RN was determined by appearance on serial magnetic resonance images (MRIs), MR spectroscopy, requirement of therapy, and development of new neurological complaints without evidence of disease progression. Therapeutic interventions for symptomatic RN included corticosteroids, bevacizumab and/or surgical resection. Patient-reported therapeutic outcomes were graded as complete response (CR), partial response (PR), and no response. Results: Twenty-six patients experienced symptomatic RN after treatment of 50 separate lesions. The mean prescription dose was 22 Gy (range, 15 to 30 Gy) in 1 to 5 fractions (median, 1 fraction). Of the 12 patients managed with corticosteroids, 6 patients (50\%) reported CR and 4 patients (33\%) PR. Of the 6 patients managed with bevacizumab, 3 patients (50\%) reported CR and 1 patient (18\%) PR. Of the 8 patients treated with surgical resection, all reported CR (100\%). Other than surgical resection, age >= 54 years (median, 54 yearsItem Long-term toxicity and survival outcomes after stereotactic ablative radiotherapy for patients with centrally located thoracic tumors(WALTER DE GRUYTER GMBH, 2020-01-01) Atalar, Banu; Mustafayev, Teuta Zoto; Sio, Terence T.; Sahin, Bilgehan; Gungor, Gorkem; Aydin, Gokhan; Yapici, Bulent; Ozyar, EnisBackground. Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastasesItem Multichannel Film Dosimetry for Quality Assurance of Intensity Modulated Radiotherapy Treatment Plans Under 0.35 T Magnetic Field(CUREUS INC, 2020-01-01) Gungor, Gorkem; Korkmaz, Latif; Kayalilar, Namik; Aydin, Gokhan; Yapici, Bulent; Mustafayev, Teuta Zoto; Atalar, Banu; Ozyar, EnisPurpose To evaluate the intensity modulated radiotherapy (IMRT) quality assurance (OA) results of the multichannel film dosimetry analysis with single scan method by using Gafchromic (TM) EBT3 (Ashland Inc., Covington, KY, USA) film under 0.35 T magnetic field. Methods Between September 2018 and June 2019, 70 patients were treated with ViewRay MRldian (R) (ViewRay Inc., Mountain View, CA) linear accelerator (Linac). Film dosimetry OA plans were generated for all IMRT treatments. Multichannel film dosimetry for red, green and blue (RGB) channels were compared with treatment planning system (TPS) dose maps by gamma evaluation analysis. Results The mean gamma passing rates of RGB channels are 97.3\% +/- 2.26\%, 96.0\% +/- 3.27\% and 96.2\% +/- 3.14\% for gamma evaluation with 2\% DD/2 mm distance to agreement (DTA), respectively. Moreover, the mean gamma passing rates of RGB channels are 99.7\% +/- 0.41\%, 99.6\% +/- 0.59\% and 99.5\% +/- 0.67\% for gamma evaluation with 3\% DD/3 mm DTA, respectively. Conclusion The patient specific QA using Gafchromic (TM) EBT3 film with multichannel film dosimetry seems to he a suitable tool to implement for MR-guided IMRT treatments under 0.35 T magnetic field. Multichannel film dosimetry with Gafchromic (TM) EBT3 is a consistent QA tool for gamma evaluation of the treatment plans even with 2\% DD/2 mm DTA under 0.35 T magnetic field presence.Item Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases(KOREAN SOC THERAPEUTIC RADIOLOGY \& ONCOLOGY, 2019-01-01) Sayan, Mutlay; Mustafayev, Teuta Zoto; Sahin, Bilgehan; Kefelioglu, Erva Seyma Sare; Wang, Shang-Jui; Kurup, Varsha; Balmuk, Aykut; Gungor, Gorkem; Ohri, Nisha; Weiner, Joseph; Ozyar, Enis; Atalar, BanuPurpose: Renal cell carcinoma (RCC) and melanoma have been considered `radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. Materials and Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. Results: We identified 53 radioresistant brain metastases (28\% RCC and 72\% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 +/- 9.5 mL and 95.5\% +/- 2.9\%, respectively. The mean prescription dose was 20 +/- 4.9 Gy. Forty lesions (75\%) demonstrated a complete/partial response and 13 lesions (24\%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. Conclusion: SRS is an effective management option with up to 75\% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.Item Magnetic Resonance Image-Guided Hypofractionated Ablative Radiation Therapy for Hepatocellular Carcinoma With Tumor Thrombus Extending to the Right Atrium(CUREUS INC, 2022-01-01) Dincer, Neris; Ugurluer, Gamze; Mustafayev, Teuta Zoto; Gungor, Gorkem; Atalar, Banu; Guven, Koray; Ozyar, EnisHepatocellular carcinoma (HCC) presenting with tumor thrombus and inferior vena cave (IVC)/right atrium (RA) infringement point to an advanced-stage disease that is deemed inoperable. Stereotactic body radiotherapy is an emerging treatment option for this group of patients with promising outcomes in recent studies that are comparable to conventional treatment methods, namely, transarterial chemoembolization and transarterial radioembolization. Here, we report a case of HCC with RA extension through the IVC. The patient was referred to our clinic for treatment options, and he was found suitable for magnetic resonance imaging-guided radiotherapy (MRgRT). We treated the patient with MRgRT in five fractions to a total dose of 40 Gray. The tumor was tracked during the treatment sessions, and adaptive treatment planning was performed before each fraction. The patient tolerated the treatment well with no acute grade 3-4 toxicities. The last follow-up showed that the patient had a complete biochemical response and is now a candidate for an orthotopic liver transplant. To our knowledge, this report is the first to document the MRgRT treatment of an HCC with TT and RA extension. MRgRT is safe and feasible for this patient group and can be an effective bridging therapy for liver transplants.Item Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity(BRITISH INST RADIOLOGY, 2021-01-01) Ugurluer, Gamze; Atalar, Banu; Mustafayev, Teuta Zoto; Gungor, Gorkem; Aydin, Gokhan; Sengoz, Meric; Abacioglu, Ufuk; Tuna, Mustafa Bilal; Kural, Ali Riza; Ozyar, EnisObjective: Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response. Methods: 50 prostate cancer patients treated with ultrahypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. Results: The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36\%, respectively. Only 6\% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade 2G1 toxicity. To date, late Grade 1 GU toxicity was experienced by 24\% of patients, 2\% of patients experienced Grade 2 GU toxicity and 6\% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. Conclusion: In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. Advances in knowledge: MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.Item Magnetic Resonance Imaging-Guided Radiation Therapy for Early-Stage Gastric Mucosa-Associated Lymphoid Tissue Lymphoma(CUREUS INC, 2022-01-01) Dincer, Neris; Ugurluer, Gamze; Gungor, Gorkem; Mustafayev, Teuta Zoto; Atalar, Banu; Ozyar, EnisLymphoid neoplasia derived from mucosa-associated lymphoid tissue (MALTItem First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience(CUREUS INC, 2019-01-01) Sahin, Bilgehan; Mustafayev, Teuta Zoto; Gungor, Gorkem; Aydin, Gokhan; Yapici, Bulent; Atalar, Banu; Ozyar, EnisObjectives Improved soft-tissue visualization, afforded by magnetic resonance imaging integrated into a radiation therapy linear accelerator-based radiation delivery system (MR-linac) promises improved image-guidance. The availability of MR-imaging can facilitate on-table adaptive radiation planning and enable real-time intra-fraction imaging with beam gating without additional exposure to radiation. However, the novel use of magnetic resonance-guided radiation therapy (MRgRT) in the field of radiation oncology also potentially poses challenges for routine clinical implementation. Herein the early experience of a single institution, implementing the first MRgRT system in the country is reported. We aim to describe the workflow and to characterize the clinical utility and feasibility of routine use of an MR-linac system. Methods The ViewRay MRIdian MR-linac system consists of a split-magnet 0.35 T MR-imaging scanner with a double focused multi-leaf collimator (MLC) equipped 6MV linear accelerator. Unique to the system are the control console integrated on-table adaptive radiation therapy (oART) planning capabilities as well as automated beam gating based on real-time intra-fraction MR imaging. From the first day of clinical implementation, oART was performed according to physicians' discretion when medically indicated. All fractions were delivered under real-time imaging with soft tissue-based automated beam gating with individualized gating boundary settings. Patients actively assisted in breath-hold beam gating with the help of custom designed prismatic glasses allowing sight of a computer monitor mounted on the back wall just behind the MRI system bore. Patient demographics and treatment experience, indications for MRgRT including diagnosis and disease site, radiation dose prescribed and fractionation scheme, utilization of oART, respiratory gating settings, as well as duration of each treatment phase were analyzed. Results Between September 2018 and May 2019, 72 patients with 84 tumor sites were treated with MRgRT in 500 total fractions. Median patient age was 66 years (range: 28-83 years). Among 84 tumor sites, the most frequently treated regions were upper abdominal and pelvic (n = 36, 43\% and n = 29, 34\%, respectively). The most common diagnosis was prostate cancer, with 14 patients treated. In 69 patients (93.2\%) oART was used at least once during a treatment course. Twenty-nine targets (43.1\%) with significant breathing-related motion were treated in breath-hold with patient visual feedback. Median prescribed dose was 36.25 Gy (range: 24-70 Gy) in median five fractions (range: 3-28 fractions). A gating boundary of 3 mm around a gating region of interest (gROI) was most commonly used (range: 3-5 mm) with 95\% of the gROI (range: 93-97\%) required to be within the gating boundary for the beam to automatically engage. Mean total treatment time was 47 min (range: 21-125 min) and mean beam-on time was 16.7 min (range: 6-62 min). Conclusions MRgRT afforded by an MR-linac system has been successfully implemented into routine clinical use at our institution as the first system of its kind in Turkey. While the overall number of patients treated and fractions delivered is still limited, we have demonstrated the feasibility of both on-table adaptive radiation therapy as well as automated real-time beam gating on a daily basis in acceptable time schedules.Item Output factors of ionization chambers and solid state detectors for mobile intraoperative radiotherapy (IORT) accelerator electron beams(WILEY, 2019-01-01) Gungor, Goerkem; Aydin, Gokhan; Mustafayev, Teuta Zoto; Ozyar, EnisPurpose The electron energy characteristics of mobile intraoperative radiotherapy (IORT) accelerator LIAC((R)) differ from commonly used linear accelerators, thus some of the frequently used detectors can give less accurate results. The aim of this study is to evaluate the output factors (OFs) of several ionization chambers (IC) and solid state detectors (SS) for electron beam energies generated by LIAC((R)) and compare with the output factor of Monte Carlo model (MC) in order to determine the adequate detectors for LIAC((R)). Methods The OFs were measured for 6, 8, 10, and 12 MeV electron energies with PTW 23343 Markus, PTW 34045 Advanced Markus, PTW 34001 Roos, IBA PPC05, IBA PPC40, IBA NACP-02, PTW 31010 Semiflex, PTW 31021 Semiflex 3D, PTW 31014 Pinpoint, PTW 60017 Diode E, PTW 60018 Diode SRS, SNC Diode EDGE, and PTW 60019 micro Diamond detectors. Ion recombination factors (k(sat)) of IC were measured for all applicator sizes and OFs were corrected according to k(sat). The measured OFs were compared with Monte Carlo output factors (OFMC). Results The measured OFs of IBA PPC05, PTW Advanced Markus, PTW Pinpoint, PTW microDiamond, and PTW Diode E detectors are in good agreement with OFMC. The maximum deviations of IBA PPC05 OFs to OFMC are -1.6\%, +1.5\%, +1.5\%, and +2.0\%