Muge Akmansu

Evaluation of nutritional status in cancer patients receiving radiotherapy: a prospective study.

Objectives:The purpose of the present study was to evaluate the nutritional status of cancer patients receiving radiotherapy (RT) and to assess the possible contributions of nutritional support to patients with malnutrition. Methods:Prospectively, 207 patients referred to our outpatient radiotherapy department were included. The patients were classified according to tumor site (head/neck, breast, lung, stomach, or colorectal). Nutritional status at the onset, at the end of RT, and 3 and 6 months after irradiation was evaluated with the subjective global assessment (SGA). All of the patients were supported with additional portions of meal or standard enteral feeding formula during and after the irradiation period as long as they were in the moderately or severely malnourished groups, respectively. Results:At the onset, malnutrition was present in 31% of all patients, and it increased to 43% at the end of RT. This difference predominated in head/neck cancer patients. Malnutrition ratios in head/neck cancer patients at the onset and after RT were 24% and 88%, respectively. By a 6-month follow-up, the ratio of patients with malnutrition decreased to 8%. Nutritional status of all groups was found to improve during the 6-month follow-up period, except for the breast cancer group, which included no patients with severe malnutrition at any time. Conclusion:The results of the present study may be helpful in planning an appropriate nutritional support for cancer patients undergoing radiotherapy according to the irradiation site.

Inhibition of epidural scar tissue formation after spinal surgery: external irradiation vs. spinal membrane application.

PURPOSE The scar tissue that forms after lumbar dissection is a severe complication and a cause of lumbar and radicular pain. It was recently shown that radiotherapy could inhibit peridural fibrosis after laminectomy. In this study, the efficiency of external irradiation was compared with spinal membrane application. METHOD AND MATERIALS Thirty male New Zealand rabbits underwent L5 laminectomy. Ten rabbits each received a single fraction of 900-cGy external irradiation administered by 9-MeV electron beam 24 h after the surgery. Ten other rabbits each had spinal membrane applied during laminectomy. The remaining 10 rabbits constituted the control group. All of the rabbits were killed 30 days after the laminectomy. Axial histologic sections through the laminectomy defect were evaluated. Each specimen was scored for the extent and density of fibrosis and arachnoidal adherence. RESULTS The extent and density of fibrosis and arachnoidal adherence differed significantly between the control group and the treatment groups (p < 0.05). However, the extent and density of fibrosis and arachnoidal adherence did not differ significantly between the spinal membrane and irradiation groups (p > 0.05). CONCLUSION This preliminary study showed that high-single-fraction/low-total-dose administered postoperatively can successfully inhibit postsurgical epidural fibrosis as effectively as applied spinal membrane.

Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide.

BACKGROUND Temozolomide is the major drug in the treatment of malignant gliomas. Radiation induced necrosis can behave radiologically and clinically like a recurrent tumor. The major problem is the differentiation between recurrence and radiation injury especially in early phases of treatment. The aim of this study was to evaluate the patients receiving temozolomide showing early clinical or radiological progression and impact of early necrosis on follow-up. PATIENTS AND METHODS We retrospectively evaluated medical records of 67 patients with malignant glioma receiving temozolomide. All patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide. In case of any radiological or clinical progression, MRI spectroscopy evaluation was used to confirm tumoral progression. RESULTS Radiological or clinical progression was observed in 17 (25.4%) patients. Early radiation induced necrosis was diagnosed in 4 of 17 patients (23.5%) by surgery (n=3) and MRI spectroscopy (n=1). The observed incidence of pseudoprogression was 4 in 67 (6%) patients. Patients with diagnosis of early radiation injury had median progression-free survival of 7 months compared to 5 months in patients without radiation damage (p=0.004). However, there was no statistically significant difference in terms of overall survival between groups. CONCLUSION Temozolomide can cause early radiation induced injury which can mimic progressive tumor. Although the discrimination between two entities results in the accurate evaluation of response to therapy and benefits those patients, it did not affect overall survival. MRI spectroscopy is a valuable tool to define early radiation necrosis and should be further evaluated in larger prospective studies.

The Risk of Radiation-Induced Carcinogenesis after External Beam Radiotherapy of Graves’ Orbitopathy

Purpose: In order to estimate the risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves’ orbitopathy, we made dosimetric measurements with thermoluminescent dosimeters in a male Rando phantom using our treatment technique. Methods: We produced dose-volume histograms from 5-mm CT slices using our treatment planning system. In this way we estimated the irradiation dose received by the main surrounding organs such as the brain, the bone and the eyeball. We use 6-MV X-ray for the treatment of Graves’ orbitopathy and our total dose is 2,000 cGy, 200 cGy per fraction. Clinical target volume was limited to the retrobulbar orbital content and medial rectus muscle, sparing the lenses, lacrimal glands and the sella turcica. All dosimetric measurements with thermoluminescent dosimeters were made 3 times. Results: We found that the dose to the right lens was 101.6 mGy and to left lens 103.4 mGy. Average absorbed doses to red bone marow, thyroid, lung, esophagus, bone surface, skin and brain, respectively, were estimated to be 523, 21, 4, 5, 81, 29, 47 mGy. Then, using tissue weighting factors specified by the International Commission of Radiation Protection, the resulting total effective dose was calculated to be 66.8 mSv. Conclusion: The risk factor for fatal cancer development derived from human epidemiological data is presently assumed to be 10% per Gy. In patients treated by our method of retro-orbital external beam radiotherapy for Graves’ orbitopathy, there is a 0.0067 (or 7 per 1,000 persons or 0.7%) risk of developing fatal radiation-induced cancer.

Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation.

Intestinal mucosal damage and bacterial translocation are clinical problems that may be caused by the use of ionizing radiation. Glutamine (Gln) support reduces the mucosal barrier in several ways. This study was undertaken to investigate the effect of timing of Gln-enriched enteral nutrition (EN) on bacterial translocation and mucosal damage due to radiotherapy (RT). A rat model of whole body irradiation was designed in which a single dose of 485 cGy was given. A total of 50 rats were randomly assigned to the following 5 groups, each of which comprised 10 rats: (1) balanced rat chow given for 8 days without RT (group 1); (2) balanced rat chow given 4 days before and 4 days after RT (group 2); (3) Gln-enriched EN given 4 days before RT (group 3); (4) Gln-enriched EN given 4 days after RT (group 4); and (5) Gln-enriched EN given 4 days before and 4 days after RT (group 5). Mesenteric lymph node and ileum samples were removed for evaluation of bacterial translocation (BT) and histopathologic investigation, respectively. BT and intestinal mucosal injury scores in all rats that received RT were higher than in rats without RT. No difference was seen in parameters between groups 3 and 4 (P>.05, P>.016, respectively); BT and intestinal mucosal injury scores of group 5 were significantly lower than those of groups 3 and 4 (P<.05, P<.016, respectively). Meanwhile, the BT and mesenteric injury scores of group 5 were significantly lower than those of group 2 (P<.05, P<.016, respectively). As a result, intestinal injury due to RT was significantly decreased by Gln-enriched EN support given before and after whole body RT.

Ultrastructural and Electrophysiologic Changes of Rat Cochlea after Irradiation

Objective/Hypothesis: To determine the acute and subacute cochlear effects of sublethal total body irradiation.

The effect of vitamin E on acute skin reaction caused by radiotherapy.

Ionizing radiation affects healthy organs and tissues as well as diseased tissues during radiation therapy. Skin reactions varying from acute erythema to necrosis can be seen. It has been found that vitamin E can prevent mutagenic and/or carcinogenic effects of ionizing radiation in both animals and cell cultures. This study investigated the preventative effect of antioxidant vitamin E on irradiation‐induced acute skin reactions. No protective effect of vitamin E was demonstrated. It is possible that the vehicle induced free radical exposure in the irradiated skin.

Temozolomide in Newly Diagnosed Malignant Gliomas: Administered Concomitantly with Radiotherapy, and Thereafter as Consolidation Treatment

Background: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was ad-ministered concomitantly with radiotherapy, and thereafter as consolidation treatment. Patients and Methods: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m2/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m2 on days 1–5 every 28 days for 6 cycles. Results: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. Conclusion: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

Gelatinase B expression as a prognostic factor in patients with stage II/III rectal carcinoma treated by postoperative adjuvant therapy.

Objective:The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival. Methods:Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint. Results:Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter. Conclusion:MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.

Prognostic Significance of Expression of CD133 and Ki-67 in Gastric Cancer

CD133 is one of the most important stem cell markers in solid cancers and Ki-67 is a marker that reflects cell proliferation. The relationships between the expression of CD133 and Ki-67 and prognosis in gastric carcinoma are unknown and need exploring. We examined 50 gastric cancer patients retrospectively in the Radiation Oncology Department of the Faculty of Medicine, Gazi University. CD133 and Ki-67 expression was examined using immunohistochemical staining. The survival rate in patients with CD133 positive expression was significantly worse than that in the patients with negative expression (p=0.04). Expression of CD133 had a positive correlation with that of Ki-67 (r=0.350; p=0.014). Multivariate analysis revealed that the expression of CD133 was an independent prognostic factor in gastric cancer (p=0.02). Conclusion, expression of CD133 may be a useful prognostic marker in gastric cancer.