Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study.

PURPOSE: To compare the incidence and severity of acute and chronic hematologic toxicity (HT) in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for curative treatment of cervical cancer and to ascertain the dosimetric parameters of two techniques associated with acute and chronic HT. MATERIALS AND METHODS: A total of 127 patients with cervical cancer receiving concomitant pelvic radiotherapy (RT) and cisplatin were evaluated. Pelvic bone marrow (BM) was contoured for each patient and divided into five sub-regions: lumbosacrum (LS), ilium (IL), lower pelvis (LP), pelvis (P), and whole pelvis (WP). The volume of each BM region receiving 10, 20, 30, and 40 Gy was calculated (V10, -V20, -V30, and -V40). The lowest level of hemoglobin, leukocyte, neutrophil, and platelet counts were obtained during chemoradiotherapy and six months after RT. The nadir values were graded according to Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Grade 2 or greater acute anemia, leukopenia, neutropenia, thrombocytopenia was observed in 2%, 41.5%, 12% ,and 0% in 3DCRT group and in 27%, 53%, 24.5%, and 4.5% in IMRT group, respectively. Grade 2 or greater chronic anemia, leukopenia, neutropenia, and thrombocytopenia was observed in 11%, 10%, 6%, and 0% in 3DCRT group and in 11%, 9%, 4.5%, and 0% in IMRT group, respectively. LS-V30, 40; IL-V10, 20, 30, 40; LP-V10, 20 ,40; P-V10, 20, 30, 40, and TP-V10, 20, 30, 40 were significantly reduced with IMRT planning compared to 3DCRT planning. Logistic regression analysis of potential predictors showed that none of the dosimetric parameters were significant for predicting acute and chronic HT. CONCLUSION: The present findings showed that IMRT planning reduced irradiated BM volumes compared to 3DCRT planning. However, no difference between the two techniques was observed in terms of acute and chronic HT. Further studies are needed to confirm these results.

An individualised treatment algorithm for tumour stage 1 glottic squamous cell carcinoma.

OBJECTIVE: To report and discuss the outcome of a treatment algorithm for patients with tumour stage 1 glottic squamous cell carcinoma. METHOD: A retrospective outcome analysis study was performed using data from a tertiary referral centre. RESULTS: Sixty-nine patients were treated with radiotherapy and 26 with surgery, in accordance with the treatment algorithm. Five-year overall survival rates were the same for both treatment groups (92 per cent). Five-year disease-specific survival rates were 100 per cent for surgery, 98 per cent for radiotherapy and 99 per cent overall. The overall 5-year laryngeal preservation rate was 89.1 per cent, being 95.7 per cent for surgery patients and 86.7 per cent for radiotherapy patients (p = 0.502). There was no significant association between laryngeal preservation rates and age (p = 0.779), anterior commissure involvement (p = 0.081), tumour stage (1a or 1b) (p = 0.266) or treatment modality (surgery or radiotherapy; p = 0.220). There was no significant difference in local recurrence rates between the two treatment groups (19.3 per cent for radiotherapy vs 10.0 per cent for surgery; p = 0.220). The overall 5-year regional recurrence rate was 1.2 per cent. CONCLUSION: Tumour stage 1 glottic carcinoma can be managed with different treatment modalities, following an individualised treatment algorithm, with results comparable to published outcomes.

Hypoxia-related molecules HIF-1α, CA9, and osteopontin : predictors of survival in patients with high-grade glioma.

PURPOSE: A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas. PATIENTS AND METHODS: HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry. RESULTS: Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028). CONCLUSION: Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer.

BACKGROUND AND PURPOSE: Survivin is one of the apoptosis inhibitor proteins. Together with Aurora B, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. PATIENTS AND METHODS: We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. RESULTS: Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. CONCLUSION: The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion.

Effects of radiation on protein oxidation and lipid peroxidation in the brain tissue.

Radiation produces reactive oxygen species that modify macromolecules such as protein and lipid by oxidation and act in many pathological processes, causing serious damage to the brain. This study sought to evaluate the effects of radiation and the protective effect of N-acetylcysteine (NAC) on the brain tissue of guinea pigs based on the levels of lipid peroxidation and protein oxidation. Thirty-two guinea pigs were divided into groups of eight animals each: control group (group I); radiation group (group II); NAC group (group III), and NAC administered before radiation exposure group; (group IV). Guinea pigs in groups II and IV were exposed to Co(60) radiotherapy using the Source-Axis-Distance = 80 technique. The levels of protein carbonyl content and malondialdehyde (MDA), which is a marker for lipid peroxidation, were investigated by the Evans-Levine and Uchiyama-Mihara methods, respectively. The protein carbonyl and MDA levels of group II were significantly greater than those of group I (P < .01). The protein carbonyl and MDA levels of group IV were lower than those of group II. The difference between the MDA levels of group IV and group II was significant (P < .01); however, the difference in protein carbonyl levels between the two groups was not significant. The results indicated that radiation increased protein oxidation and lipid peroxidation in the brain, and NAC administration before radiation exposure may aid in the treatment by decreasing protein and lipid oxidation.

Preserving effects of melatonin on the levels of glutathione and malondialdehyde in rats exposed to irradiation.

In this study we investigated whether pretreatment with melatonin was protective against the injury of the central nervous system (CNS) in rats receiving LD(50) whole body irradiation. The wistar rats were randomized into four groups: i) the control group (CG), ii) melatonin-administered group (MG; 1 mg/kg body weight), iii) irradiated group (RG; 6.75 Gy, one dose), and iv) melatonin-administered and irradiated group (MRG). Blood samples were drawn from the rats 24 h after the treatment and plasma glutathione levels were assayed. Plasma glutathione level was significantly higher in RG than CG. The melatonin pretreatment prevented GSH increase induced by irradiation. Lipid peroxidation and glutathione levels of rat cerebral cortex were determined in all groups after 24 h. Cortical malondialdehyde (MDA) was significantly higher in the RG. The melatonin pretreatment prevented cortical MDA increase induced by irradiation. Cortical GSH was significantly lower in RG than the CG. The melatonin pretreatment prevented cortical GSH decrease induced by irradiation. Tissue samples were obtained from cerebral cortex and hypothalamus which also were affected by ionizing irradiation in the CNS and were evaluated with electron microscopy. Histopathological findings showed that LD(50) whole body irradiation resulted in damage of the neuronal cells of CNS. The results obtained from this study demonstrated that pretreatment with melatonin prevented the damage that develops in CNS following irradiation. The beneficial effect of melatonin can be related to protection of the CNS from oxidative injury and preventing the decrease in the level of cortical glutathione.

Melatonin treatment for prevention of oxidative stress: involving histopathological changes.

This study was undertaken to test the effect of irradiation on the histopathology of the hypothalamus and cerebral cortex. In addition, the probable effects of radiotherapy on the activities of antioxidant enzymes and levels of nitric oxide (NO) in the plasma were investigated as well. The effects of melatonin treatment on radiotherapy-based central nervous system (CNS) damage were also studied. For this purpose, the rats were randomized into four groups. The first group was the control group (sham-exposed group), the second group received only melatonin, the third group was irradiated and the fourth group received both melatonin and irradiation. Plasma samples of rats were collected for measuring the activities of superoxide dismutase (SOD), catalase (CAT) and the levels of NO. 24 h after the interventions, tissue samples were obtained from the hypothalamus and the cerebral cortex for the light microscopic investigations. These tissues were mostly affected by radiation. The results indicated that the application of radiation significantly enhanced the levels of plasma SOD and NO. On the other hand, melatonin pretreatment prevented the decrease in plasma CAT activity induced by irradiation. It was found that the application of melatonin could significantly prevent the irradiation-induced damages. Light microscopic results revealed that the damage of the CNS by radiation was prevented by the application of melatonin.

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.

Role of free radicals on mechanism of radiation nephropathy.

PURPOSE: In our study, after applying a single dose of 612 cGy irradiation, we aimed to observe the role of free radicals on tissue damage in the kidney caused by radiation by measuring NO level, Na/K-ATPase activity and TBARS amount which is an indicator of free radical damage. On the other hand we investigated whether the tissue damage can be prevented by vitamin A or not. MATERIALS AND METHODS: This study was performed on three groups: 1. Control group 2. The group to which irradiation was administrated 3. The group which was given radiation + vitamin A. The irradiation group of animals were given a single dose of gamma irradiation at a sublethal dose. In the group which was administrated both irradiation + vitamin A, vitamin A was given for two days prior to irradiation. The amount of NO was measured by ESR spectroscopy, Na/K-ATPase and TBARS were measured by spectrophotometry. RESULTS AND CONCLUSIONS: As a result of radiation mediated tissue damage in the kidney, we observed a NO loss, a decrease in Na/K-ATPase activity and an increase in TBARS amount. Although the administration of vitamin A before radiation, did not have any effect on NO loss and decrease in Na/K-ATPase.

Results of chemoirradiation after curative resection of locally advanced gastric cancer.

To evaluate the results of post-operative chemoirradiation for gastric carcinoma. The records of 58 patients who underwent resection for gastric carcinoma were retrospectively reviewed. Forty-six patients had complete resection without any residual disease but with high-risk factors of relapse. Twelve patients had microscopic residual disease. Doses of irradiation ranged from 45 to 54 Gy with a median dose of 49 Gy in 1.8 Gy fractions. Fifty-three of the patients received 5-fluorouracil-based concomitant chemoradiotherapy, and all of them received chemotherapy after the completion of radiotherapy. The median survival of the entire group of patients was 21 months. The 30th month disease-free and overall survival after surgery was 32 and 45%, respectively. The median survival time and 30th month survival rate was 23 months and 54% in patients with no residual disease, and 15 months and 18% for those with residual disease, respectively (p = 0.049). A statistically significant correlation was detected between residual disease and survival and between high-grade tumour and survival (p < 0.05 for each). Patients with both nodal involvement and direct tumour extension beyond the gastric wall have a high risk of locoregional failure, and adjuvant chemoradiotherapy reduces local failure and improves survival.

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.

Intracerebral malignant fibrous histiocytoma in a 5-year-old girl.

A case of primary intracerebral malignant fibrous histiocytoma (MFH) in 5-year-old girl is presented, the eighteenth case so described in modern literature. A lobulated, heterogenous mass lesion with a haemorragic component was present in our case' s MRI. A review of the literature on MFH of the pediatric age group was done to establish guidelines for standard treatment modalities in primary intracerebral MFH.

Treatment of age-related subfoveal neovascular membranes by teletherapy: results of a non-randomized study.

This investigation was designed to determine whether low-dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularization. Thirty-one patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 12 Gy of 6MV X-rays, and 72 patients who were untreated served as a control group. Both groups were followed-up. At six months of follow-up visual acuity was maintained in 54.8% and improved 25.8% of patients treated by radiotherapy. In the control group, visual acuity showed deterioration in 55.5%. There was a significant difference between the treated and untreated groups (p < 0.01). Significant neovascular membrane regression or stabilization was recorded in 61.3% of treated patients at six months post-radiation, whereas the membranes in all. 72 control patients showed progressive enlargement. This non-randomized study suggested that low doses of radiation may be an alternative treatment for ARMD without an immediate drop in visual acuity or significant radiation morbidity.

Atypical acute reaction associated with radiotherapy: a case report.

Radiation therapy may cause acute and/or chronic skin reactions. In this paper a patient with contact urticaria associated with irradiation is described. We could not determine the agent behind the contact urticaria in our patient in light of the current literature. We are reporting this case because the literature neither mentioned radiotherapy as being among the agents that lead to contact urticaria nor reported contact urticaria as being among the acute reactions to radiotherapy.

External radiotherapy in macular degeneration: our technique, dosimetric calculation, and preliminary results.

PURPOSE: This study was performed to determine the toxicity and efficacy of external-beam radiotherapy in patients with age-related subfoveal neovascularization. METHODS AND MATERIALS: Between January 1996 and September 1996, 25 patients with a mean age of 70.5 (60-84) years were enrolled. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. A total of 25 patients were treated with a total dose of 12 Gy in 6 fractions over 8 days. We used a lens-sparing technique and patients were treated with a single lateral 6-MV photon beam. To assess the risk of radiation carcinogenesis after treatment of age-related subfoveal neovascularization, we estimated the effective dose for a standard patient on the basis of tissue-weighting factors as defined by the International Commission on Radiological Protection (ICRP). The calculations were made with TLD on a male randophantom. The lens dose was found to be 0.217 Gy per fraction. RESULTS: No significant acute morbidity was noted. Visual acuity was maintained or improved in 76% and 80% of treated patients at their 1- and 3-month follow-up examinations, respectively. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 23 patients (92%) at 3 months after irradiation. CONCLUSION: Our observations on these 25 patients in this study indicate that many patients will have improved or stable vision after radiotherapy treatment with low-dose irradiation.

Adult Wilms' tumour. A report of two cases and their treatment and prognosis.

Adult Wilms' tumour, unlike that seen in childhood, is a rare disease. We report on two patients of whom one is alive with no evidence of disease at 65 months of follow-up and the other had no evidence of disease at 10 months when she was lost to follow-up. The literature has been reviewed and the prognosis and treatment alternatives are presented.

Adult Wilms tumour. A report of two cases and their treatment and prognosis.

Adult Wilms tumour, unlike that seen in childhood, is a rare disease. We are reporting two cases of which one is alive with no evidence of disease at the 52nd month of follow-up and the other had no evidence of disease at the 10th month after which she was lost to follow-up. The literature has been reviewed and the prognosis and treatment alternatives have been surveyed.