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.

Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases.

OBJECTIVES: In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern. PATIENTS AND METHODS: A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT. RESULTS: A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements. CONCLUSION: Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

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.

Results of Chordoma Patients Treated by Different Approaches in a Single Institution.

AIM: To discuss the optimal and recent treatment options based on clinical review of 16 chordoma patients. MATERIAL AND METHODS: Data of the patients diagnosed and treated between 1999 and 2017 in Gazi University School of Medicine has been collected through patients’ files and the electronic database of hospital records. Statistical analysis was applied to evaluate the correlation between the progression free survival and treatment modalities. RESULTS: Nine of the 16 patients were women (56.3%). Half of the patients had intracranially located tumors, whereas the other 50% of the sample had spinal (n=5) and sacral (n=3) chordomas. The median follow-up time was 51.7 months. Recurrence was observed in 50% of patients, while the median recurrence time equaled to 27.6 months. Multivariate analysis results showed that age, gender tumor size, intra or extracranial location of tumor, treatment modalities, subtotal or grosstotal resection of tumor, radiotherapy dose, and techniques were not associated with recurrence. On the other hand, 2 patients are still under chemoterapy (imatinib, bevacizumab) without evident of recurrent disease. CONCLUSION: Despite the fact that surgery remains to be the cornerstone of treatment, total resection is not reasonable for all patients with chordomas. For this reason, adjuvant treatment for ensuring local control is highly important. If the residual tumor is of a small volume, SBRT may provide more advantages. Targeted treatment or chemotheapeutic agents may also be benificial for maintanence therapy. As the clinical awareness about chordomas is based on our series, aggressive multi-modality treatment options should be applied in the adjuvant therapy.