Prognostic Significance of Two Dimensional AgNOR Evaluation in Local Advanced Rectal Cancer Treated with Chemoradiotherapy.

The prognostic significance of AgNOR proteins in stage II-III rectal cancers treated with chemoradiotherapy was evaluated. Silver staining was applied to the 3µm sections of parafin blocked tissues from 30 rectal cancer patients who received 5-FU based chemoradiotherapy from May 2003 to June 2006. The microscopic displays of the cells were transferred into the computer via a video camera. AgNOR area (nucleolus organizer region area) and nucleus area values were determined as a nucleolus organizer regions area/total nucleus area (NORa/ TNa). The mean NORa/TNa value was found to be 9.02±3.68. The overall survival and disease free survival in the high NORa/TNa (>9.02) patients were 52.2 months and 39.4 months respectively, as compared to 100.7 months and 98.4 months in the low NORa/TNa (<9.02) cases. (p<0.001 and p<0.001 respectively). In addition, the prognosis in the high NORa/TNa patients was worse than low NORa/TNa patients (p<0.05). In terms of overall survival and disease-free survival, a statistically significant negative correlation was found with the value of NORa/TNa in the correlations tests. Cox regression analyses demostrated that overall survival and disease-free survival were associated with lymph node status (negative or positive) and the NORa/TNa value. We suggest that two-dimensional AgNOR evaluation may be a safe and usable parameter for prognosis and an indicator of cell proliferation instead of AgNOR dots.

Contribution of involved-field radiotherapy to survival in patients with relapsed or refractory Hodgkin lymphoma undergoing autologous stem cell transplantation.

OBJECTIVES: To assess the outcomes of overall survival and posttransplantation survival in patients with Hodgkin lymphoma (HL) undergoing autologous stem cell transplantation (ASCT) because of the development of relapse or resistance after chemotherapy (CT) or CT plus radiotherapy (combined modality treatment, CMT). METHODS: Forty-five patients undergoing ASCT because of the development of relapse or resistance after CT or CMT for HL were enrolled in the study. Radiotherapy was given as involved-field radiotherapy. Patients were treated with CT alone (n=25) or CMT (n=20). These 2 groups were further divided into 2 subgroups: the patients with early-stage (I to II) and advanced-stage (III to IV) HL. RESULTS: Median patients age was 29 years (range, 16 to 60 y) and the median follow-up was 60 months (range, 12 to 172 mo). In the patients with advanced-stage HL, there was no statistically significant difference in overall survival between irradiated and nonirradiated patients (n=18, irradiated n=4 and nonirradiated n=14). However, in the patients with early-stage disease, there was a significant difference in 5- and 10-year overall survival between the irradiated and nonirradiated groups (81% vs. 48% and 66% vs. 24%, respectively, P=0.045; n=26, irradiated n=16 and nonirradiated n=10). In the univariate analysis, irradiated group and involvement of 1 to 2 nodal regions were found to be significant for overall survival, whereas irradiated group, early stage, and involvement of 1 to 2 nodal regions were found to be significant for posttransplantation survival. However, only irradiated group was found to be significant for posttransplantation survival in multivariate analysis (P<0.05). CONCLUSIONS: Addition of involved-field radiotherapy to CT in patients undergoing ASCT after relapse or recurrence failed to provide survival benefit in patients with advanced HL, while a survival benefit was observed in patients with early-stage HL. Radiotherapy should be considered as part of CMT in the patients with early-stage HL, which should not be neglected.

Effect of an oral mucositis protocol on quality of life of patients with head and neck cancer treated with radiation therapy.

This study was conducted to determine the effect of an oral mucositis prevention protocol on nutritional status and quality of life for patients undergoing radiation therapy for head and neck cancers. This randomized, controlled, experimental study placed 20 patients in an intervention group where they received an oral care protocol and a nutrition protocol. Thirty patients were placed in the control group. Data were collected through face-to-face interviews using an oral assessment guide, oral evaluation guidelines, an oral toxicity scale, a visual analog scale, a subjective global assessment index, and a quality-of-life scale. As time post-treatment progressed, the prevalence of malnutrition in the intervention group was lower than in the controls group, and the intervention group experienced significantly less pain related to oral mucositis. Similar deteriorations in quality of life were noted in each group.

An institutional experience of quality assurance of a treatment planning system on photon beam.

AIM: The purpose of the present study is to show the application of the IAEA TRS-430 QA procedures of Eclipse™v7.5 TPS for photon energies. In addition, the trends of the deviations found in the conducted tests were determined. BACKGROUND: In the past, the lack of complete TPS QA procedures led to some serious accidents. So, QA in the radiotherapy treatment planning process is essential for determination of accuracy in the radiotherapy process and avoidance of treatment errors. MATERIALS AND METHODS: The calculations of TPS and measurements of irradiations of the treatment device were compared in the study. As a result, the local dose deviation values (δ 1: central beam axis, δ 2: penumbra and build up region, δ 3: inside field, δ 4: outside beam edges, δ 50-90: beam fringe, RW50: radiological width) and their confidence limit values (including systematic and random errors) were obtained. RESULTS: The confidence limit values of δ 4 were detected to increase with expanding field size. The values of δ 1 and δ 3 of hard wedge were larger than open fields. The values of δ 2 and δ 50-90 of the inhomogeneity effect test were larger, especially than other tests of this study. The average deviation was showed to increase with the rise of the wedge angle. The values of δ 3 and δ 4 of lung irradiation were outside tolerance. CONCLUSIONS: The QA of TPS was done and it was found that there were no reservations in its use in patient treatment. The trend of the deviations is shown.

Is human kallikrein-11 in gastric cancer treated with surgery and adjuvant chemoradiotherapy associated with survival?

Human kallikreins (hKs) have been reported to be involved in human cancers, and several hKs are promising biomarkers of various cancers, such as prostate, ovarian, breast, and testicular cancer. In the present study, we aimed to evaluate the prognostic value of immunohistochemical expression of hK11 in patients with gastric cancer. The study included 55 (36 men and 19 women; 58 ± 10 years of mean age) patients with gastric cancer treated with surgery and adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-hK11 antibody. Of the 55 patients, 35 (63.6%) were hK11-positive and 20 (36.4%) were hK11-negative. Disease-free and overall survival rates were significantly higher in patients with hK11 positive than in those with hK-11 negative expression (24 months vs. 11 months, p: 0.043; 29 months vs. 13 months, p: 0.038, respectively). In conclusion, hK11 expression in gastric cancer appears to be associated with a better prognosis. hK11 may be a prognostic biomarker of gastric cancer. On the other hand, it is needed to elucidate the mechanisms underlying the regulation of hK11 expression in gastric cancer.

Whole abdominal field versus standard field radiotherapy plus concomitant and adjuvant chemotherapy for patients with locally advanced gastric cancer.

PURPOSE: To compare standard radiotherapy field (SRTF) with whole abdomen irradiation (WAI), used in conjunction with adjuvant chemotherapy following curative surgery in patients with gastric cancer. METHODS AND MATERIAL: Ninety patients were included in the study and divided into two treatment arms. In the first treatment arm, SRTF, including 45 Gy radiation to the primary tumor and regional lymph nodes, was performed in 45 patients. In the second treatment arm, a total of 45.2 Gy RT was delivered; 20 Gy to the whole abdomen followed by 25.2 Gy RT to the tumor and regional lymph nodes, in 45 patients. An intravenous bolus dose of 250 mg/m(2)/week 5-fluorouracil (5-FU) was administered concomitantly with RT in both treatment arms. Patients who completed concomitant chemoradiotherapy, received adjuvant treatment, including 4 cycles of 5-FU (425 mg/m(2)) and folinic acid (20 mg/m(2)) in 4 week intervals. RESULTS: Median age was 56 years (range: 22-81), 89% of the patients (n = 80) had serosal involvement, 78% (n = 70) were node positive. The rate of hematological (40% vs. 16%, p = 0.010) and gastrointestinal toxicities (80% vs. 53%, p = 0.010) were higher, and performance loss (60% vs. 29%, p = 0.003) was greater in the second treatment arm. Number of patients who experienced Grade 3 and Grade 4 gastrointestinal toxicities (especially diarrhea) were higher in the second treatment arm (4% vs. 16%, p = 0.049). The median follow-up was 19 months (range: 7-96). The median 5-year survival was 29% and 17%, locoregional control was 30% and 25%, and disease-free survival was 27% and 16% in the first and second treatment arms, respectively. There was no significant difference between the treatment groups in terms of survival, locoregional control and disease-free survival rates (p > 0.05). CONCLUSION: Whole abdomen irradiation was not found to be superior to standard field radiotherapy used in conjunction with adjuvant chemotherapy in gastric cancer.

Prognostic significance of CD9 expression in locally advanced gastric cancer treated with surgery and adjuvant chemoradiotherapy.

The tetraspanin transmembrane protein CD9 plays an important role in inhibiting cell motility in numerous neoplastic cell lines, including lung, gastric, pancreatic, and bladder carcinomas. The prognostic importance of CD9 in the survival of gastric carcinoma patients has not been examined to date, and in the present study, we attempted to define its prognostic value. The study included 49 (35 men and 14 women) patients with locally advanced (stages II-IV) gastric cancer. The median age was 55 years (range, 22-73 years). Surgery was the initial treatment for all patients, followed by adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-CD9 antibody. Of the 49 patients with gastric adenocarcinoma, 11 (22.4%) were CD9-positive, and 38 (77.6%) were CD9-negative. A significant prognostic value in disease-free survival and overall survival was observed in T classification and CD9 positivity. In conclusion, CD9 expression in gastric cancer appears to be associated with poor prognosis.

Which urine marker test provides more diagnostic value in conjunction with standard cytology- ImmunoCyt/uCyt+ or Cytokeratin 20 expression.

BACKGROUND: Because of the poor sensitivity of urinary cytological findings for the diagnosis of especially low grade urinary bladder carcinoma, new molecular diagnostic methods have been proposed. We decided to verify the ImmunoCyt/uCyt+ (UCyt+) test and cytology combination and cytokeratin 20 (CK20) and cytology combination in urine as possible diagnostic and monitoring tool for bladder cancer. METHODS: Evaluation of CK20 expression and UCyt+ was performed in urine of 90 patients of which 54 with bladder cancer with primary/recurrent diagnosis (low grade urothelial carcinoma (LGUC) = 23/8 patients, high grade urothelial carcinoma (HGUC) = 18/5 patients), and 36 patients as control; except of neoplastic bladder disease patients. For the evaluation of the three tests, CK20 and UCyt+ tests were combined with urine cytology and compared with each other. RESULTS: The overall sensitivity detected for each tumor marker was as follows: for urine cytology was 75.9% and UCyt+ was 83.3%, for CK20 70.4%, while the specificity was 66.7% for urine cytology and 86.1% for UCyt+ and 83.3% for CK20. The sensitivity of cytology and UCyt+ combination was higher (88.9%) than the sensitivity cytology and CK20 combination (77.8%). The simultaneous use of the three markers, sensitivity was reaching 92.5%. CONCLUSION: The UCyt+ test and CK20 expression are valid tools for the performance of adjunctive analyses with conventional cytologic examination.

Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats.

PURPOSE: The prevention of radiation-induced pulmonary toxicity may help to improve radiation therapy in the cancer patient. The aim of this study was to investigate the pulmonary protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on radiation-induced lung injury in rats. METHODS: 30 Wistar albino rats were divided into three groups and treated with saline, Radiation (RT) and RT + CAPE respectively. All rats were treated with CAPE (50 ?mol/kg i.p.) or saline. The first dose of CAPE was injected 24 h before radiation and application continued daily, with radiation in second day and 2 days more after the radiation treatment. Radiation dose was 800 cGy for total body. At 72 hr after the last radiation application, under general anesthesia using ip ketamine, the lungs were removed immediately after decapitation. After sacrification, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) activities and malondiadehyde (MDA) levels were evaluated in lung tissue. RESULTS: The level of malondialdehyde (MDA) was higher in the RT group (233.4+/-1.5 nmol/g protein) than in both the control (131.8+/-0.92) and the RT + CAPE (151.4+/-1.8) groups (P < 0.001). However, CAT activity was decreased in the RT group (7.26+/-0.27 U mg protein) compared with control (8.49+/-0.51) and increased again in the RT + CAPE group (8.31+/-0.56; P < 0.001). In accord with CAT activity, SOD activity in the RT group (0.42+/-0.07 nmol MDA/g wet tissue) was different from the control (0.78+/-0.02) and RT + CAPE (0.86+/-0.06) groups (P < 0.001). CONCLUSION: CAPE application with radiation therapy attenuated radiation induced pulmonary injury in vivo, possibly by its antioxidant effect.

Aminoguanidine ameliorates radiation-induced oxidative lung damage in rats.

PURPOSE: To investigate the possible protective effects of aminoguanidine (AG ) on lung damage in whole body irradiated rats. METHODS: To evaluate the biological damage of radiation on rat lung tissue, lipid peroxidation products were measured using biochemical parameters. Thirty Wistar albino rats were divided into three subgroups: control (C) , irradiation alone (RT), and RT + AG combined. After sacrificing the rats, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities and malondiadehyde (MDA), nitric oxide (NO) levels were evaluated in lung tissue. RESULTS: Administration of AG resulted in an increase in the activities of CAT, SOD and GSHPx in the lungs. All were reduced after radiation. In addition, AG administration resulted in a decrease in both NO and MDA levels in lung compared with the irradiated group. CONCLUSION: Amnoguanidine increased the endogenous antioxidant defence mechanism in rats and protected the animals from radiation-induced lung toxicity. Moreover, AG may protect against ionizing radiation-induced lung damage because of its antioxidant effect.

Experimental posterior perforating ocular injury in rabbit eyes: effects of radiotherapy with or without intravitreal cyclosporin on vitreous proliferation.

Double perforating ocular injuries were made in 30 rabbits and the effects of radiotherapy (RT) alone or in combination with cyclosporin (CS) on vitreous proliferation investigated. Thirteen rabbits in group 1 received RT alone (600 cGy), and 13 rabbits in group 2 received RT combined with 100 microg of intravitreal CS. No treatment was given to 4 rabbits in the control group (group 3). All animals were ophthalmologically examined on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings scored; they were sacrificed on the 28th day, and histopathological scoring was made. The median histopathological score of the RT group (4.0; range: 0-8) was significantly higher than that of the CS + RT group (1.0; range: 0-5; p = 0.018). We conclude that intravitreal CS may be used as an adjunctive agent to RT to inhibit intraocular proliferation following penetrating ocular injury in rabbits.

The role of c-erbB-2 expression on the survival of patients with small-cell lung cancer.

The aim of this study was to determine the incidence and role of c-erbB-2 overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males; median age- 56.5 yr, range-34-75) all of whom had adequate tissue specimens available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2 overexpression. Seventy-five of the cases were positive for c-erbB-2, had extensive disease. The median overall survival of patients with SCLC whose tumors were positive and negative for c-erbB-2 were 8 +/- 0.9 months (95%CI 6.3-9.7) and 11 +/- 1.5 months (95%CI 8.0-14.0), respectively. c-erbB-2 overexpression detected using immunohistochemistry is observed in 17.9% of patients with SCLC and has statistically significant prognostic value. Our findings suggest that c-erbB-2 may be a potential target for site-specific immunotherapy in SCLC. Considering one technique examined, further molecular investigation is needed to confirm these preliminary findings.

Radiotherapy after surgery for benign cerebral meningioma.

BACKGROUND AND PURPOSE: To compare the outcome from adjuvant and delayed radiotherapy (RT) after surgery in patients with benign cerebral meningioma. PATIENTS AND METHODS: Between March 1953 and January 2001, 92 patients with benign cerebral meningioma (WHO grade I) were treated with surgery. Forty-eight patients underwent gross total resection (GTR), and 44 patients underwent subtotal resection (STR). Treatments were classified as GTR (n = 48), STR+adjuvant RT (n = 12), STR alone (n = 32). The prognostic factors were assessed as, gender, the Karnofsky performance score (KPS) (> or =90 vs. <90), the extent of surgery, and adjuvant or delayed RT. The endpoints analyzed were progression-free survival (PFS) and overall survival (OS). Overall survival curve of the study population is compared with the age-adjusted expected survival curve for the US population born in 1970. RESULTS: The median follow-up was 7.7 years. The 5-year PFS and OS rates for all patients were 65 and 93%, respectively. The 5-year PFS rates in patients treated with GTR and STR were 77 and 52%, respectively (P = 0.02). Patients treated with STR+adjuvant RT had significantly better PFS (91%) at 5 years than with STR alone (38%) (P = 0.0005). Gender showed no statistically significant impact on either PFS or OS (P > 0.05). However, multivariate analysis showed the KPS to have a statistically significant effect on OS (P = 0.02). The OS rate was the same across all three treatment groups. The age-adjusted expected survival curve for the US population born in 1970 lay within the confidence intervals for the overall survival curve of the study population. CONCLUSIONS: Although OS was not affected, adjuvant RT appeared to significantly reduce tumor progression. However, only a prospective randomized trial can adequately determine whether adjuvant or delayed radiotherapy is the better approach in patients with subtotally resected benign meningioma.

Intracranial meningeal hemangiopericytoma: the role of radiotherapy: report of 29 cases and review of the literature.

BACKGROUND: The current retrospective study was undertaken to evaluate the treatment outcomes of patients with meningeal hemangiopericytoma (M-HPC), to define the role of radiotherapy in the management of the disease, and to report on the patterns of failure. METHODS: The medical records of 29 patients with nonmetastatic M-HPC treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between August 1979 and March 1999 were reviewed. Fifteen patients (52%) underwent macroscopic total resection ('gross total resection' [GTR]), 10 (34%) underwent subtotal resection (STR), and 4 (14%) had unknown extent of surgery. Ten of 24 patients received adjuvant radiotherapy. RESULTS: The 5, 10, and 15-year overall survival rates were 85%, 68%, and 43%, respectively. The local control rates at 5 and 10 years were 68% and 22%, respectively. Two patients experienced disease recurrence at another intracranial site. Sixteen patients (55%) developed extraneural metastases. Four patients (14%) developed spinal metastases. The 5-, 10-, and 15-year distant metastasis-free survival rates were 80%, 46%, and 21%, respectively. The 5-year local control rates for patients treated with GTR and STR were 84% and 38%, respectively (P=0.003). Of the 15 patients treated with GTR, 3 received adjuvant radiotherapy as part of their initial treatment. Malignant disease did not recur locally in these three patients. However, the effect of the adjuvant radiotherapy on local control was not statistically significant. CONCLUSIONS: M-HPCs can recur locally or distantly in the neural axis or as extraneural distant metastases. Based on literature review and the patterns of failure in the current series, attempting to perform GTR followed by limited-field radiotherapy appeared to represent a reasonable approach for the initial management of M-HPC.