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Item Current treatment strategies in malignant pleural mesothelioma with a treatment algorithm(VIA MEDICA, 2019-01-01) Sayan, Mutlay; Eren, Mehmet Fuat; Gupta, Apar; Ohri, Nisha; Kotek, Ayse; Babalioglu, Ibrahim; Kaplan, Sedenay Oskeroglu; Duran, Ozge; Or, Ozlem Derinalp; Cukurcayie, Funda; Kurtul, Neslihan; Bicakci, Beyhan Ceylaner; Kutuk, Tugce; Senyurek, Sukran; Turk, Ali; Jabbour, Salma K.; Atalar, BanuMalignant pleural mesothelioma (MPM) is a rare disease with a poor prognosis. The main therapeutic options for MPM include surgery, chemotherapy, and radiation therapy (RT). Although multimodality therapy has been reported to improve survival, not every medically operable patient is able to undergo all recommended therapy. With improvements in surgical techniques and systemic therapies, as well as advancements in RT, there has been a potential new paradigm in the management of this disease. In this review, we discuss the current literature on MPM management and propose a functional treatment algorithm.Item The Impact of Everolimus and Radiation Therapy on Pulmonary Fibrosis(MDPI, 2020-01-01) Eren, Mehmet Fuat; Eren, Ayfer Ay; Sayan, Mutlay; Yucel, Birsen; Elagoz, Sahende; Ozguven, Yildiray; Vergalasova, Irina; Altun, Ahmet; Kilickap, Saadettin; Daliparty, Vasudev Malik; Bese, NuranBackground and objectives:Everolimus (EVE) is a mammalian target of the rapamycin (mTOR) inhibitor that is widely used in cancer patients. Pulmonary toxicity, usually manifesting as interstitial pneumonitis, is a serious adverse effect of this drug. Radiation therapy, which is often administered in conjunction with chemotherapy for synergistic effects, also causes pulmonary fibrosis. In view of pulmonary damage development in these two forms of cancer treatment, we have examined the effect of EVE administration individually, in combination with radiation given in varying sequences, and its relation to the extent of pulmonary damage.Materials and Methods:We performed an experimental study in albino rats, which were randomized into five groups: (1) control group, (2) EVE alone, (3) EVE 22 h after radiation, (4) EVE 2 h after irradiation, and (5) only radiation. Sixteen weeks after thoracic irradiation, rat lung tissue samples were examined under light microscopy, and the extent of pulmonary damage was estimated. After this, we calculated median fibrosis scores in each group.Results:The highest fibrosis score was noted in Group 4. Among the five groups, the control group had a significantly lower median fibrosis score compared to the others. When the median fibrosis score of the group that received concurrent EVE with radiation therapy (RT) (Group 4) was compared with that of the control group, the difference was statistically significant (p= 0.0022). However, no significant differences were achieved among the study groups that received EVE only or RT only, whether concurrently or sequentially (p> 0.05).Conclusion:EVE is an effective treatment option for the management of several malignancies and is often combined with other therapies, such as radiation, for a more efficient response. However, an increased risk of pulmonary fibrosis should also be anticipated when these two modalities are combined, as they both can cause pulmonary damage, especially when administered concurrently.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 Patient-Reported Tolerance of Magnetic Resonance-Guided Radiation Therapy(FRONTIERS MEDIA SA, 2020-01-01) Sayan, Mutlay; Serbez, Ilkay; Teymur, Bilgehan; Gur, Gokhan; Zoto Mustafayev, Teuta; Gungor, Gorkem; Atalar, Banu; Ozyar, EnisPurpose Magnetic resonance-guided radiation therapy (MRgRT) has been incorporated into a growing number of clinical practices world-wide, however, there is limited data on patient experiences with MRgRT. The purpose of this study was to prospectively evaluate patient tolerance of MRgRT using patient reported outcome questionnaires (PRO-Q). Methods Ninety patients were enrolled in this prospective observational study and treated with MRgRT (MRIdian Linac System, ViewRay Inc. Oakwood Village, OH, United States) between September 2018 and September 2019. Breath-hold-gated dose delivery with audiovisual feedback was completed as needed. Patients completed an in-house developed PRO-Q after the first and last fraction of MRgRT. Results The most commonly treated anatomic sites were the abdomen (47\%) and pelvis (33\%). Respiratory gating was utilized in 62\% of the patients. Patients rated their experience as positive or at least tolerable with mean scores of 1.0-2.8. The most common complaint was the temperature in the room (61\%) followed by paresthesias (57\%). The degree of anxiety reported by 45\% of the patients significantly decreased at the completion of treatment (mean score 1.54 vs. 1.36,p= 0.01). Forty-three percent of the patients reported some degree of disturbing noise which was improved considerably by use of music. All patients appreciated their active role during the treatment. Conclusion This evaluation of PROs indicates that MRgRT was well-tolerated by our patients. Patients' experience may further improve with adjustment of room temperature and noise reduction.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.