The Assessment of Clinical Outcomes and Prognostic Factors in Glioblastoma Patients.

AIM: To assess the outcomes of glioblastoma patients treated in our clinic over the last 10 years using a multimodality approach and cutting-edge techniques. MATERIAL AND METHODS: In our study, we included 169 glioblastoma patients who were admitted to our clinic between 2009 and 2019 and received concurrent radiotherapy (RT) + temozolomide (TMZ) after surgery. Patients were collected retrospectively and analyzed using appropriate statistical methods. RESULTS: The average follow-up period was 19 months. The average overall survival (OS) was 20.5 months. PFS and PPS were found to be 10.8 and 8.9 months, respectively. In the multivariate analysis for prognostic factors on OS, the Karnofsky Performance Score (KPS), the extent of resection (EOR), and the use of adjuvant TMZ were significant. PFS was significantly predicted by KPS, EOR, adjuvant TMZ, and planning target volume (PTV). Acute severe lymphopenia (ASL) following RT reduced the OS and PFS. There was no statistical difference in OS, PFS, recurrence patterns, or ASL incidence between the RTOG and EORTC regimens and RT techniques (IMRT vs. 3D-CRT). The association between dose-volume parameters (V3, V5, V10, V15, and V20 and V25, V30, V40, and V60 Gy) and post-treatment ASL frequency was studied. For each parameter, threshold levels were discovered. Furthermore, patients with recurrent glioblastoma who received salvage therapies had better outcomes. CONCLUSION: A multidisciplinary, and intensive treatment approach using modern techniques improved the OS of glioblastoma patients. Furthermore, in glioblastoma patients, larger RT fields were not associated with better outcomes. As a result, lymphocytesparing RT may be more beneficial in increasing patients' compliance to adjuvant TMZ, which is an important prognostic factor of OS.

Acute Effects of Manual Lymphatic Drainage and Compression with Exercise Therapy on Breast Lymphedema Following Breast-Conserving Surgery and Radiotherapy.

Background: Breast lymphedema is a common complication of breast cancer treatments but there are limited studies about the treatment of breast lymphedema. The aim of this study was to investigate the acute effects of manual lymphatic drainage (MLD), compression with exercise on the local tissue water percentage, pain, and stiffness following breast-conserving surgery and radiotherapy. Materials and Methods: Twenty-two patients (52.54 ± 12.18 years, 28.55 ± 5.11 kg/m2) were included. The sociodemographic and clinical information was recorded. The pain and stiffness severity were measured with Visual Analog Scale. Measurements of water percentages in local tissue were performed in all quadrants of the breast with the Moisture Meter D Compact device. All measurements were performed baseline, after MLD, and after compression with exercise. Results: There was a significant difference in local tissue water percentages between the affected and unaffected sides before treatment. The percentage of water only in the lower outer quadrant of the affected breast increased significantly after acute treatment (p: 0.002). In addition, pain (p: 0.001) and stiffness (p: 0.001) scores decreased. Conclusions: Local tissue water percentages increased with MLD and decreased with compression with exercise. In the treatment of breast lymphedema, MLD and compression bandage with exercise may be beneficial in the management of the symptoms of swelling, pain, and stiffness.

Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis.

BACKGROUND: The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. MATERIALS AND METHODS: Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-ß1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-ß1 levels was examined before and after the experiment. RESULTS: After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-ß1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-ß1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-ß1 dramatically decreased. CONCLUSIONS: Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.

A Comparison of Ramipril and Bevacizumab to Mitigate Radiation-Induced Brain Necrosis: An Experimental Study.

BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS). METHODS: A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression). RESULTS: The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols. CONCLUSIONS: Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood-brain barrier.

Prophylactic Bevacizumab May Mitigate Radiation Injury: An Experimental Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is widely used to treat brain pathologies alone or in concert with other treatment modalities. However, there are some side effects, such as radiation injury characterized by edema and necrosis in peripheral tissues, that must be managed. A new treatment agent against this side effect is bevacizumab, which targets increased vascular endothelial growth factor (VEGF) as a prominent etiologic factor in radiation injury. In this study, we created a rat experimental model to describe the effects of both radiation and the anti-VEGF monoclonal antibody bevacizumab following high-dose SRS, and to compare the effects of prophylactic and delayed-onset bevacizumab treatment. METHODS: Fifty-four adult male Wistar rats were allocated into 9 groups based on differing Gamma-knife surgery (GKS) doses and bevacizumab treatment protocols. After 12 weeks, the rats' right frontal lobes were examined with hematoxylin and eosin staining and immunohistochemistry analysis via VEGF and CD31 antibodies. RESULTS: Radiation necrosis occurred to varying degrees in all irradiated animals between 3 and 10 weeks post-SRS. Higher GKS dose (50% isodose of 100 Gy) led earlier necrosis and prophylaxis of bevacizumab at this dose was associated with delayed onset of necrosis. Moreover, prophylactic bevacizumab mitigated the effects of radiation necrosis following GKS at both doses, whereas this effect was not prominent with late initiation of bevacizumab (treatment protocol). CONCLUSIONS: Our findings show that the onset and degree of radiation injury are affected by the GKS dose and protocol of bevacizumab administration.

The evaluation of the feasibility of carotid sparing intensity modulated radiation therapy technique for comprehensive breast irradiation.

PURPOSE: To investigate the feasibility of carotid sparing intensity modulated radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries for comprehensive irradiation of breast cancer patients who have risk factors for atherosclerosis. The dose distribution of CS-IMRT technique and the conventional irradiation technique were also compared. PATIENTS AND METHODS: Ten patients who were previously treated with comprehensive three-dimensional conformal radiation therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans were compared in terms of conformity index, homogeneity index, and the doses to organ at risk and carotid arteries. RESULTS: The homogeneity and conformity indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the carotid arteries were reduced by applying CS-IMRT without compromising the target volume coverage. When the carotid artery was considered as organ at risk for CS-IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT plans (p=0.017). The median of the maximum dose to the carotid artery was decreased under 50Gy with CS-IMRT. CONCLUSIONS: CS-IMRT can significantly reduce the unnecessary radiation dose to the carotid arteries compared with conventional 3DCRT technique while maintaining target volume coverage. CS-IMRT technique can be considered for breast cancer patient with high risk of atherosclerosis.

Radiotherapy applications of patients with malignant mesothelioma: A single center experience.

BACKGROUND: In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms. AIM: The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma. MATERIALS AND METHODS: Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy. RESULTS: Prophylactic radiation was applied to 27 patients with 4-15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6-18 MV photon and/or 4-12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases. CONCLUSION: Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes.

Radiological report: expectations of clinicians.

PURPOSE: Although there have been many publications on composing an accurate radiological report, they usually do not include an assessment of the clinicians' expectations from a radiological report. In this study, we aimed to assess the clinicians' expectations and preferences in terms of radiology report style and content. MATERIALS AND METHODS: A multiple-choice questionnaire, containing 19 questions, was formed. Two-hundreds clinicians, working either in a university hospital or a public hospital, were allocated into 4 groups which included equal number of clinicians from surgery and internal medicine departments. Questionnaire was applied to participants by face-to-face interview. Results were analyzed for each group using Pearson chi-square test. RESULTS: No statistically significant difference was found among four groups except for the 16th question which was about the image format pertaining to the report (CD/DVD or negative film). It has been determined that clinicians preferred detailed, standardized radiological reports with complete sections (i.e., clinical information, technique, findings, conclusion, recommendations). CONCLUSION: This study provided essential data for radiologists to write more effective reports.

The histopathologic evaluation of soft tissue changes in rabbit extremity after different dose-fractionation schemes of interstitial high dose rate (HDR) brachytherapy.

BACKGROUND: The use of HDR in the treatment of soft tissue sarcoma had been on the rise. However, there was limited study to evaluate the effect of different fractionation schemes on soft tissue and the optimal HDR scheme. AIMS: We aimed to assess the histopathologic changes on soft tissue after different HDR brachytherapy doses. METHODS: The subjects were divided into three groups. Each group included 10 limbs. Group A had only an applicator without radiation, group B received a total of 24 Gy at 6 Gy per fraction, twice a day, and group C received a total of 13.5 Gy in a single fraction. The histopathologic findings were grouped into soft tissue pathology-1 (edema, inflammation, endothelial proliferation, necrosis) and soft tissue pathology-2 (atrophy, calcification, vascular hyalinization, fibrosis) (STP-1-2). RESULTS: The highest mean grade values of STP-1 and STP-2 were observed in group C (0.95 and 1.45) in comparison to group A (0.45 and 0.85) and group B (0.65 and 0.9). The difference in STP-1 was found significant only between groups A and C and the difference in STP-2 was found both between groups A and C and groups B and C. CONCLUSION: In our experimental study it was shown that the fractionated interstitial HDR had both lower rate and severity of toxicity in comparison to a single high dose fraction. Before using a single fractionated regimen in the clinic, the increased morbidity related to the irreversible early toxicities or progressive late toxicities should be kept in mind.

Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis.

AIMS AND BACKGROUND: Glioblastoma is the most common primary brain tumor in adults. The standard treatment is surgery and radiotherapy. In this study, the results of radiotherapy plus concomitant and adjuvant temozolomide are reported. In addition, the efficiency of adjuvant temozolomide is evaluated. METHODS AND STUDY DESIGN: Forty-one patients were analyzed. All patients received radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after surgery. Thirty-one patients received an average of 6 cycles (range, 1-8 cycles) of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose of 200 mg/m2/day. The primary end point was overall survival. RESULTS: The median overall survival was 16.7 months. The overall survival significantly increased in the adjuvant temozolomide group compared to the group with no adjuvant therapy (18.9 vs 9.8 months). The difference in overall survival between adjuvant temozolomide cycles of < or = and > 3 was significant (8.7 vs 20 months). On multivariate analyses, the important prognostic factors were type of surgery and application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy, respectively. CONCLUSIONS: The study confirmed the effectiveness of radiotherapy plus temozolomide in newly diagnosed glioblastoma. It was established that the application of adjuvant temozolomide for at least 4 cycles is required to obtain a benefit from adjuvant therapy. However, further studies are needed to confirm these data.

Primary cardiac angiosarcoma: a case report.

Primary tumors of the heart are rarely seen. Cardiac angiosarcomas are malignant tumors that almost always have a poor prognosis. We describe a 29-year-old man with primary cardiac angiosarcoma with multiple site metastases. The therapeutic approach includes surgery, chemotherapy and radiotherapy alone or in combination. New techniques of radiotherapy and combined chemotherapeutic agents may relieve symptoms and prolong a patient's life. We discuss the diagnosis and treatment of cardiac angiosarcoma in the light of a case report.