Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy.

PURPOSE: The purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis. METHODS: Forty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments. RESULTS: BV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN. CONCLUSION: The use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.

Clinical factors, management, and outcomes of children under 3 years old with central nervous system tumors: single-center experience.

PURPOSE: Children under 3 years old represent a notable portion, about 25 to 30%, of all central nervous system tumor (CNS) cases. Their clinical course, prognosis, and treatment significantly differ from older children. This single-center retrospective study aims to comprehensively analyze survival factors in children under three diagnosed with CNS tumors. METHODS: Between April 2012 and December 2023, cases under 3 years of age with CNS tumors diagnosed at our center were retrospectively evaluated. RESULTS: Among 279 CNS tumor cases, 42 (15%) were evaluated. The 5-year overall and event-free survival rates were 67.4% (95% CI 47.5-81.1) and 39.8% (95% CI 24.2-55.0), respectively. Gender, symptom onset to diagnosis time, pathological neurological findings at diagnosis, and tumor location did not significantly impact survival (p > 0.05). However, cases with neurological symptoms showed significantly higher event-free survival rates (p < 0.05). Patients with embryonal tumors, metastases, inability for total surgical excision, relapsed/progressive diseases, and who under 1 year old had significantly lower survival rates (p < 0.05). Radiotherapy timing did not affect survival (p > 0.05). Event-free survival rates remained unchanged after the third year. CONCLUSION: The current treatments have been observed to have a positive impact on survival rates. Nonetheless, there is a need for novel treatments for patients with embryonal tumors, metastases, aged under 1 year, and those where total surgical excision is not feasible or in cases with progressive/relapse disease. This study underscores the importance of the first 3 years regarding relapse, progression, or mortality risk.

Effects of testosterone treatment on recovery of rat spermatogenesis after irradiation.

OBJECTIVE: To determine the effects of two different radiation doses on sperm parameters and the role of testosterone treatment on rat spermatogenesis. METHODS: The experimental animal study was conducted at Marmara University, Istanbul, Turkey, from September 2012 to January 2013. Male Sprague Dawley 4-6 months old rats weighing 300-350g were randomely divided into 5 equal groups as control, low dose irradiation, testosterone administration following low dose irradiation, high dose irradiation, and testosterone administration following high dose irradiation. The animals were kept at a constant temperature in a room with 12h light and dark cycles. After the group-wise intervention, sperm concentration, testicular size, and histopathological examination of seminiferous tubules were noted. SPSS 10 was used for statistical analysis. RESULTS: The 40 rats in the study were divided in 5 groups of 8(20%) each. In low dose radiation, adverse effects were only temporarily observed with the return of almost normal testicular function at the end of two months with or without testosterone supplementation. In contrast, in high dose radiation, hormonal treatment effect was controversial. CONCLUSIONS: Testosterone treatment had no significant effect upon recovery after irradiation. In order to prevent the untoward effects of radiation, shielding of the remaining testis in a proper manner is crucial to avoid the harmful effects of the scattered radiation.

Radiation pneumonitis in relation to pulmonary function, dosimetric factors, TGFß1 expression, and quality of life in breast cancer patients receiving post-operative radiotherapy: a prospective 6-month follow-up study.

PURPOSE: To investigate development of radiation pneumonitis (RP) in relation to pulmonary function, dosimetric factors, and transforming growth factor beta-1 (TGFß1) expression in irradiated breast cancer patients. METHODS: A total of 49 breast cancer patients who received post-operative radiotherapy (RT) were evaluated in terms of pulmonary function tests (PFTs), quality of life (QoL), development of RP, dosimetric factors, cytokine levels, and lung high-resolution computed tomography (HRCT) before and after RT. ROC analysis was performed for performance of dosimetric factors in predicting RP, while frequencies of single nucleotide polymorphisms (SNPs) genotyped for TGFß1 (rs11466345 and rs1800470) were also evaluated. RESULTS: All cases with RP (10.2%) recovered clinically at the end of third post-RT month. PFT and HRCT parameters were similar before and after RT overall, as well as by RP and the radiation field subgroups. ROC analysis revealed the significant role of the ipsilateral V5 (cutoff value of 45.9%, p = 0.039), V10 (29.4%, p = 0.015), V20 (23%, p = 0.017), and MLD (1200 cGy, p = 0.030) in predicting RP. Higher post-RT TGFß1 levels (p = 0.037) were noted overall and in patients with RP. Patient and control groups were similar in terms of frequencies of SNPs genotyped for TGFß1 (rs11466345 and rs1800470). EORTC QLQ-C30 and QLQ-BR-23 scores were similar in patients with vs. without RP. CONCLUSION: Our findings revealed significant role of dosimetric factors including MLD, V20 as well as the low dose-volume metrics in predicting the risk of RP among breast cancer patients who received post-operative RT. Implementation of RT, extent of radiation field or the presence of RP had no significant impact on PFTs.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated rare tumor. Median overall survival is usually between 8 and10 months, with a 1-year survival rate of 20%. Conventional anthracycline based chemotherapy regimens demonstrate low response rates with short duration. Novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape of ATC have been investigated. CASE PRESENTATION: We herein report the rechallenge of a 52-year-old ATC patient with BRAF V600E mutation with dabrafenib plus trametinib. She presented with recurrent and progressive disease despite surgery, radiation therapy, 3 different chemotherapy regimens, and combination of dabrafenib-trametinib in different settings. She was rechallenged with dabrafenib-trametinib, and had a good response. CONCLUSION: To our knowledge, this is the first ATC case who responded to dabrafenib-trametinib rechallenge, reported in the literature. We want to emphasize that combination of dabrafenib and trametinib might be a good choice for resistant locoregional and metastatic ATC patients with BRAF V600E mutation, particularly in whom rapid clinical response is urgently needed. Moreover, rechallenge with this combination should be kept in mind in selected cases.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Prognostic value of modified Glasgow prognostic score in recurrent high-grade glial tumors treated with systemic treatment.

OBJECTIVES: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor. We aimed to evaluate the prognostic value of modified Glasgow Prognostic Score (mGPS), which is combination of C-reactive protein (CRP) and albumin, in recurrent high-grade glioma patients treated with systemic treatment. PATIENTS AND METHODS: Data of 85 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. Patients were grouped according to mGPS criteria: mGPS-0: CRP < 10 mg/L and albumin >3.5 g/dL; mGPS-1: CRP < 10 mg/L and albumin <3.5 g/dL or CRP > 10 mg/L and albumin >3.5 g/dL; and mGPS-2: CRP > 10 mg/L and albumin <3.5 mg/L. We investigated the prognostic role of mGPS groups, mutations and survival outcomes. RESULTS: There were 42 (49.4 %), 25 (29.6 %), and 18 (21 %) patients in mGPS-0, mGPS-1, and mGPS-2 groups, respectively. Median follow-up duration was 10 months (1-70 months). Median OS was 8.1 months. According to mGPS-0, -1 and -2; median OS was 13.8 months, 7.3 months and 3.6 months respectively (p = 0.003). mGPS, ATRX and IDH-1 mutation status, and ECOG PS were found to be independent prognostic factors for OS. CONCLUSION: In our study, mGPS was found to be an independent prognostic factor in patients with recurrent high-grade gliomas. If validated, mGPS can be used as an objective, easily calculated, cheap, and readily available prognostic model in routine practice.

Clinical and prognostic features of plasmacytomas: a multicenter study of Turkish Oncology Group-Sarcoma Working Party.

To identify the outcomes of prognostic factors of solitary plasmacytoma mainly treated with local radiotherapy (RT). The data were collected from 80 patients with solitary plasmacytoma (SP). Forty patients (50.0%) received radiotherapy (RT) alone while 38 of them (47.5%) were treated with surgery (S) and RT. The median radiation dose was 46 Gy (range 30-64). The median follow up was 2.41 years (range 0.33-12.33). Ten-year overall survival (OS) and local relapse-free survival (LRFS) were 73% and 94%, respectively. The median progression-free survival (PFS) and multiple myeloma-free survival (MMFS) were 3.5 years and 4.8 years, respectively. On multivariate analyses, the favorable factors were radiotherapy dose of > or =50 Gy and RT + S for PFS and younger age for MMFS. For the patients with medullary plasmacytoma, the favorable factor was younger age for MMFS. RT at > or =50 Gy and RT + S may be favorable prognostic factors on PFS. Younger patients, especially with head-neck lesion and without pre-RT macroscopic tumor, seem to have the best outcome when treated with RT +/- S. Progression to MM remains as the main problem especially for older patients.

Resveratrol treatment may preserve the erectile function after radiotherapy by restoring antioxidant defence mechanisms, SIRT1 and NOS protein expressions.

Radiotherapy (RT) for prostate cancer (PC) can cause erectile dysfunction (ED) by damaging neurovascular structures with oxidative stress. In this study, we evaluated the effects of resveratrol, an antioxidant, on post-RT ED. Fifty rats in five groups were evaluated; control (C), prostate-confined radiotherapy with short- and long-term vehicle or resveratrol treatment. Cavernosal tissues were obtained to analyze glutathione (GSH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), 8-hydroxy-2'-deoxy-guanosine (8-OHdG) levels and superoxide dismutase (SOD), caspase-3 activities, sirtuin-1, Foxo-3, nNOS, and eNOS protein expressions. Intracavernosal pressures (ICP) were measured for the long-term treatment group. In the RT + long-term vehicle treatment group, tissue GSH, NO, cGMP, and SOD activity were decreased while 8-OHdg levels and caspase-3 activities were increased. Radiotherapy caused a decrease in sirtuin-1, nNOS, and eNOS protein expressions. These parameters were reversed by resveratrol treatment. Foxo-3 protein expressions were unaltered in the RT + short-term vehicle treatment group and started to increase as a defense mechanism in the RT + long-term vehicle group; however, resveratrol treatment caused a significant increase in Foxo-3 expressions. Resveratrol preserved the metabolic pathways involved in erectile function and provided functional protection. Resveratrol can be used as a supplementary agent in patients undergoing radiotherapy to preserve erectile function.

Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H&N-35 modules.

PURPOSE: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. PATIENTS AND METHODS: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoL scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. RESULTS: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on QoL, whereas concomitant chemotherapy adversely affected 5 symptom scores. CONCLUSION: Quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined therapies. The factors that adversely affect quality of life are advanced tumor stage, female gender, and long-term follow-up. Further controlled studies to evaluate both preradiotherapy and postradiotherapy status are necessary to clarify the contribution of each treatment modality to QoL.

Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats.

This study was designed to study the effects of the potential radioprotective properties of pharmacological doses of melatonin against organ damage induced by whole-body irradiation (IR) in rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC producing 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anaesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 mg/kg and 10 mg/kg, i.p.) and decapitated at 12-h after exposure to irradiation. Another group of rats was followed for 72-h after IR, where melatonin (10 mg/kg, i.p.) injections were repeated once daily. Tissue levels of malondialdehyde (MDA)--an index of lipid peroxidation--, glutathione (GSH)--a key to antioxidant--and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were estimated in liver, lung, colon and intestinal tissues. The results demonstrate that both 12-h and 72-h following IR, tissue levels of MDA were elevated (p<0.05-0.001), while GSH levels were reduced (p<0.05-0.001) in all organs. On the other hand, melatonin, reduced the levels of MDA and increased the GSH levels significantly, (p<0.05-0.001). MPO activity was increased significantly in the colonic tissue at the both 12-h and 72-h, and in the hepatic tissue at the 72-h following IR, which were reduced by melatonin (p<0.01-0.001). In the lung tissue enzyme activity was decreased at 72nd h of post-irradiation. In conclusion, the increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in irradiation-induced tissue damage, and melatonin, by its free radical scavenging and antioxidant properties, ameliorates irradiation-induced organ injury. Thus, supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy.

F-18 FDG PET/CT findings of primary sinonasal hemangiopericytoma: rare location in a young adult patient.

Hemangiopericytoma is an unusual tumor that arises from vascular smooth muscle cells. It is mainly experienced in 4th to 5th decades of life and soft-tissue masses are frequently located in lower extremity, pelvis, and retroperitoneum. A 29-year-old man presented with a mass lesion in the right nasal cavity associated with shortness of breath as a result of nasal obstruction. An incisional biopsy was reported as sinonasal type hemangiopericytoma. The initial staging F-18 flourodeoxyglucose PET/CT successfully demonstrated severe hypermetabolism in the primary tumor location and mild-to-moderate hypermetabolism in the right upper jugular lymph node.

Concomitant chemoradiotherapy with low-dose weekly gemcitabine for nonmetastatic unresectable pancreatic cancer.

BACKGROUND/AIMS: This study aimed to demonstrate the efficacy and tolerability of low-dose weekly gemcitabine as a radiosensitizer in unresectable pancreatic cancer patients treated with chemoradiotherapy. METHODS: Twenty-four histologically confirmed pancreatic carcinoma patients (female/male: 10/14, median age: 60) were evaluated. Seven (29%) patients received gemcitabine either as a single agent or in combination prior to chemoradiotherapy. Concurrent 75 mg/m2 gemcitabine was infused weekly. Radiotherapy was delivered to the primary tumor and positive lymphatics with 3D-conformal radiotherapy to a total dose of 4500 cGy. Local progression-free survival, distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier method. RESULTS: Median follow-up was 36 weeks. Median local progression-free survival, distant metastasis-free survival and overall survival were 22 weeks (95% confidence interval [CI]: 5-59 weeks), 19 weeks (95%CI: 6.9-31 weeks) and 36 weeks (95%CI: 28-43 weeks), respectively. All patients completed radiotherapy as scheduled. Concurrent gemcitabine was given fully in 58.3% of patients. Gemcitabine was terminated in four (16.6%) patients due to grade 3 neutropenia (n=1), grade 3 nausea/vomiting (n=2) or patient's reluctance (n=1). Patients with local response and stable disease to chemoradiotherapy revealed a median survival of 39 weeks (95%CI: 30-47.9 weeks) compared to 36 weeks (95%CI: 9.7-62.2 weeks) in patients with locally progressive disease (p=0.52). Pain was improved in 50% of patients. CONCLUSIONS: Weekly low-dose radiosensitizing gemcitabine is effective and safe in unresectable pancreatic cancer patients.

Ginkgo biloba extract protects against ionizing radiation-induced oxidative organ damage in rats.

The present study was designed to determine the possible protective effects of Ginkgo biloba extract (EGb) against oxidative organ damage induced by irradiation (IR). Sprague-Dawley rats were exposed to whole-body IR (800 cGy) after a 15-day pretreatment with either saline or EGb (50 mg/kg/day), intraperitoneally, and treatments were repeated immediately after the IR. Then the rats were decapitated at either 6 h or 72 h after IR, where EGb or saline injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde, glutathione levels, myeloperoxidase activity and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH)-an indicator of tissue damage and TNF-alpha were assayed in serum samples. In the saline-treated irradiation groups, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the tissues (p < 0.01-0.001), which were in parallel with the increases in luminol and lucigenin CL values. In the EGb treated-IR groups, all of these oxidant responses were prevented significantly (p < 0.05-0.01). LDH and TNF-alpha levels, which were increased significantly (p < 0.01-0.001) following IR, were decreased (p < 0.05-0.001) with EGb treatment. In conclusion, the present data demonstrate that EGb, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that EGb may have a potential benefit in enhancing the success of radiotherapy.