Yildiz Guney

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Cases of glioblastoma multiforme metastasizing to spinal cord

Cases of glioblastoma multiforme (GBM) metastasizing to the leptomeninx or the intramedullary spine are quite rare and prognoses are relatively poor. We present three cases of GBM with spinal metastasis, one of which also had leptomeningeal dissemination. Three patients with GBM were admitted to our clinic for postoperative radiotherapy after surgery. Leptomeningeal metastasis and dissemination were diagnosed with magnetic resonance imaging. Radiotherapy provided only temporary relief from pain with small improvement in neurological deficit but no survival advantage.

Comparison of Early Oncological Results of Diode Laser Surgery with Radiotherapy for Early Glottic Carcinoma

Objective To evaluate the oncologic results of transoral endolaryngeal microscopic diode laser surgery (MDLS) and radiotherapy (RT) for T1 and T2 glottic carcinoma. Study Design Case series with planned chart review. Setting Ankara Oncology Education and Research Hospital. Subjects and Methods The study was conducted on a series of 140 cases of early glottic carcinoma (T1, T2) treated with MDLS or RT. The tumors were defined according to T stage and the involvement of the anterior commissure (AC). Results The 3-year locoregional control rate of MDLS and RT groups was 93.1% and 89.7%, respectively (P = .434). There was no difference in 3-year disease-free survival when comparing T1 and T2 tumors treated with MDLS and those treated with RT (P = .618 for T1, P = .084 for T2). There was no difference in disease-free survival when comparing AC– and AC+ tumors treated with MDLS and those treated with RT (P = .291 for AC– and P = .530 for AC+ tumors). Conclusions Microscopic diode laser surgery in early glottic cancer seems to be an oncologically safe procedure that has similar oncological results with RT. In T2 glottic tumors and AC involvement, the results with either treatment are less satisfactory.

Lack of a time-dependent effect of melatonin on radiation-induced apoptosis in cultured rat lymphocytes

Ionizing radiation is widely used for the treatment of solid tumors and it is thought to act by directly targeting tumor clonogens, also known as stem cells. Apoptosis is a genetically programmed mechanism of cell death often characterized by internucleosomal DNA cleavage. Although it has been previously shown that lymphocytes readily undergo apoptosis in patients receiving anticancer drugs or treatment with ionizing radiation, this is the first study to investigate the influence of radiotherapy and melatonin on apoptosis in rat lymphocytes at two different times of the day. Melatonin, a free radical scavenger, is an endogenous neurohormone predominantly synthesized in and secreted by the pineal gland. It has been shown that melatonin inhibits apoptosis in normal cells but it increases the rate of apoptosis in various cancer cells. Therefore, in the present study, the effect of melatonin on apoptosis in cultured lymphocytes was studied after total body irradiation (TBI) was given to rats in the morning (1 HALO) or evening (13 HALO) with morphological and DNA fragmentation analysis. Two‐way analysis of variance (ANOVA) revealed that radiation increased the rate of apoptosis in rat lymphocytes after TBI, and melatonin treatment did not reduce the rate of apoptosis after TBI at either time point. We conclude that the lack of an effect of melatonin on the apoptosis rate in rat lymphocytes might be due to the dose‐dependent effect of melatonin, the time course of apoptosis investigated, or the cell type in which apoptosis was examined.

Adjuvant Radiotherapy for Gastric Carcinoma: 10 years Follow-up of 244 cases from a Single Institution

BACKGROUND Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Reirradiation with Robotic Stereotactic Body Radiotherapy for Recurrent Nasopharyngeal Carcinoma

BACKGROUND Recurrent nasopharyngeal carcinoma (NPC) after previous radiotherapy is challenging. There is no standard approach for salvage treatment. Here we present toxicity and treatment results for recurrent NFC patients who underwent fractionated stereotactic radiotherapy (FSRT) as second line radiotherapy (RT). MATERIALS AND METHODS Between April 2009 and July 2012, 24 patients, with a male to female ratio of 3:1, were treated with CykerKnife® FSRT for recurrent NFC in our institution. Seven out of 24 patients had metastatic recurrent disease. Median age was 53 years (range, 20-70 years). Initial RT dose was 70Gy. The time period between initial RT and FSRT was a median of 33.2 months. The median prescription dose for FSRT was 30Gy (range, 24-30 Gy) in a median of 5 fractions (range, 4-6). RESULTS The median follow-up for all patients was 19.5 months (IQR: 12.2. -29.2 months). The locoregional control; progression free survival and overall survival (OS) rates for 1-, 2- and 3-year were 64%, 38%, 21%; 60%, 30%, 17% and 83%, 43%, 31%, respectively. Median OS for the entire cohort was 22 months (95% CI: 16.5-27.5). On multivariate analysis recurrent tumor stage was the only prognostic factor for OS (p=0.004). One patient exhibited grade III temporal lobe necrosis. One died because of grade IV mucositis and overlapping infection. CONCLUSIONS The treatment of recurrent NPC is controversial. Fractionated stereotactic radiotherapy is promising. However, the published trials are heterogeneous with respect to the selection criteria and treatment details. Prospective studies with long term follow-up data are warranted.

Optic nerve glioma treatment with fractionated stereotactic radiotherapy

In the current report, the authors present a case of optic nerve glioma treated with fractionated stereotactic radiotherapy (FSRT). An 11-year-old girl was referred to our clinic with increasing proptosis over a 1-year period. At that time orbital MRI revealed a 20 × 17-mm mass in the right retroorbital lipomatous tissue, and FSRT was delivered to the tumor using the CyberKnife. During the 1.5-year follow-up, ophthalmological examinations did not indicate any treatment-related severe toxicity, and posttreatment MRI demonstrated marked regression of the lesion to 13 × 10 mm. Given the scarcity of reports on this subject, the authors support more extended studies of the CyberKnife for the effective treatment of this relatively common childhood tumor.

Gliosarcoma: a study of four cases

Gliosarcomas (GS) are highly malignant and rare tumors of the central nervous system with a poor prognosis. We report here on four patients with GS, the median survival for whom was 9.25 months. Prognosis of GS remains poor, and a multidisciplinary approach (surgery, radiation therapy, and chemotherapy) seems to be associated with slightly more prolonged survival times.

Whole Brain Radiotherapy Combined with Stereotactic Radiosurgery versus Stereotactic Radiosurgery Alone for Brain Metastases

BACKGROUND The aim of this study was to evaluate the effect of whole brain radiotherapy (WBRT) combined with streotactic radiosurgery versus stereotactic radiosurgery (SRS) alone for patients with brain metastases. MATERIALS AND METHODS This was a retrospective study that evaluated the results of 46 patients treated for brain metastases at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiation Oncology Department, between January 2012 and January 2015. Twenty-four patients were treated with WBRT+SRS while 22 patients were treated with only SRS. RESULTS Time to local recurrence was 9.7 months in the WBRT+SRS arm and 8.3 months in SRS arm, the difference not being statistically significant (p= 0.7). Local recurrence rate was higher in the SRS alone arm but again without significance (p=0,06). CONCLUSIONS In selected patient group with limited number (one to four) of brain metastases SRS alone can be considered as a treatment option and WBRT may be omitted in the initial treatment.