Could Amifostine Prevent Experimental Radiotherapy-Induced Acute Pericarditis?

BACKGROUND: Amifostine is a powerful antioxidant that is one of the documented three chemo-radio prototectants recommended for clinical use. There is no data exploring amifostine in prevention of acute pericardial damage. We aimed to investigate whether amifostine has protective effect against acute pericardial injury due to radiotherapy in an experimental rat model. METHODS: Twenty-four rats were divided into four groups: control group, radiotherapy-only group, amifostine-only group, radiotherapy+amifostine group. In groups receiving radiotherapy, hearts were irradiated with a Co 60 teletherapy device at a distance of 80 cm and 20 Gy at a depth of 2 cm. Thirty minutes before interventions, 200 mg/kg amifostine or same volume 0.9% NaCl were administered intraperitoneally. Subjects were sacrificed 24 hours after the procedure. Pericardial histopathological changes were investigated by light microscopy. RESULTS: There was focal inflammation of >= 50% in all rats exposed-to-radiotherapy. All groups receiving radiotherapy revealed a significant increase in pericardial inflammation compared to the groups that did not receive irradiation (p<0.05). There was no difference between the radiotherapy-only group and amifostine+radiotherapy group for pericardial inflammatory response (p>0.05). CONCLUSION: Acute pericarditis was detected in all rats receiving radiotherapy. There was no positive effect of amifostine administration before radiotherapy on acute pericardial inflammation.

Dosimetric comparison of different treatment planning techniques with International Commission on Radiation Units and Measurements Report-83 recommendations in adjuvant pelvic radiotherapy of gynecological malignancies.

AIM: The study evaluates the different treatment planning techniques according to three recommendation levels of the International Commission on Radiation Units and Measurements Report-83 in gynecologic cancer patients treated with adjuvant pelvic radiotherapy (APR). MATERIALS AND METHODS: Computerized tomography images of ten endometrial and cervical cancer patients who were treated with APR were assessed. For each patient, five different treatment plans were created. One homogeneity index and four different conformity indexes (CIs) were calculated for three-dimensional conformal radiotherapy (3D-CRT), field-in-field (FIF), seven-field intensity modulated radiotherapy (7-IMRT) with two different degrees beginning (7A-IMRT, 7B-IMRT) and 9-IMRT treatment plans. Dose volume histogram parameters and normal tissue complication probability (NTCP) were compared for organs at risk (OAR). RESULTS: The CI values of the IMRT were closer to 1 with respect to other plans (P < 0.05). The rectum and the bladder volumes which received more than 40 Gy were decreased with IMRT compared to 3D-CRT (P < 0.05). Doses received by the 195 cc volume of the small intestine and NTCP values were significantly decreased with IMRT (P < 0.05). CONCLUSION: IMRT provided more protection than FIF plans at high dose volumes of the OAR; however, it did not show any superiority at low-dose volumes. The NTCP results supported IMRT for only small intestine protection. Because IMRT is increasingly used clinically, the comparison of NTCP will become more common in the near future. Therefore, new prospective studies with sufficient number of patients and appropriate NTCP models are needed for this treatment modality.

Long-term results of a concomitant boost radiotherapy technique for elderly patients with muscle-invasive bladder cancer.

OBJECTIVES: To evaluate the long-term clinical efficacy and toxicity of concomitant boost radiotherapy (CBRT) in elderly patients with invasive bladder cancer. METHODS AND MATERIALS: Elderly patients (n=188; mean 75-year-old, range 70-91 years; 88.3% male/11.7% female) with T1-T4a bladder carcinoma were irradiated with CBRT. A total of 24 (12.8%) patients were diagnosed at stage T1, 117 (62.2%) were at stage T2, 28 (14.9%) at were stage T3a, 14 (7.4%) were stage T3b, and 5 (2.7%) were stage T4a. A dose of 45Gy in 1.8Gy fractions was administered to the whole pelvis 5 days/week over 5 weeks. A concomitant boost limited to the bladder tumor area plus margin or whole bladder of 22.5Gy in 1.5Gy fractions was administered from weeks 3×5. Thus, irradiation totalled 67.5Gy over 5 weeks. The interfraction interval was ≥6h/treatment day. We assessed prognostic factors for overall survival (OS), cause-specific survival (CSS) and relapse-free survival (RFS). RESULTS: Median follow-up was 46.2 months (range 4.7-155.7 months). Median overall survival was 27 months (95% CI:21-33 months). In this study, 146 (77.7%) patients had complete response, 39 (20.7%) had residual disease and 4 (1.6%) had progressive disease. The mean 3-, 5- and 10-year OS rates were respectively 41.2% (S.E.±0.036), 29% (S.E.±0.034), and 13.8% (S.E.±0.031). Significant prognostic factors for OS and CSS, by multivariate analysis, were tumor T-stage and urothelial obstruction. CONCLUSION: This CBRT protocol provided excellent results with a high complete response rate and good tolerance. This approach may therefore be particularly appropriate for elderly patients with invasive bladder cancer.

Long-term outcomes in treatment of invasive bladder cancer with concomitant boost and accelerated hyperfractionated radiation therapy.

PURPOSE: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. METHODS AND MATERIALS: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. RESULTS: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. CONCLUSIONS: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma.

BACKGROUND: When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group. METHODS: Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes. RESULTS: In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% +/- 28.4%, mean CTV decreased by 38.7% +/- 24.7%, mean PTV1 decreased by 31.1% +/- 23.1%, and mean PTV2 decreased by 40.0% +/- 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients. CONCLUSION: This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.

Cranial prophylactic irradiation in locally advanced non-small cell lung carcinoma: current status and future perspectives.

As a result of improved local and regional control with aggressive multimodality protocols, the brain has become one of the major sites of relapse in patients with locally advanced non-small cell lung carcinoma (LA-NSCLC). The demonstrated efficacy of prophylactic cranial irradiation (PCI) in small-cell lung carcinoma led to studies of its effectiveness in LA-NSCLC, which indicated that PCI also has a high potential to reduce the incidence or delay the occurrence of brain metastases in this patient group. This report provides an extensive review of the current evidence from nonrandomized and randomized trials regarding the use of PCI in LA-NSCLC and discusses related key issues including risk factors, patient selection criteria, timing of PCI, preferred PCI dosing scheme, toxicity profile and potential novel PCI techniques.

Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters.

BACKGROUND: The purpose of this study was to evaluate the efficacy of oral glutamine in the prevention of acute radiation-induced esophagitis (ARIE) and weight loss in lung carcinoma patients, and to determine the clinical/dosimetric predictors of ARIE. PATIENTS AND METHODS: Data from 41 patients with stage III lung carcinoma treated with thoracic irradiation were retrospectively analyzed. Twenty-two patients (53.6%) received prophylactic powdered glutamine in doses of 10g/8h. Prescribed radiation dose to planning target volume was 60Gy, in 30 fractions, 5 days/week. The primary endpoint included the ARIE incidence and its correlation with clinical/dosimetric factors relative to treatment with glutamine. RESULTS: Glutamine was well tolerated. Grade 2 or 3 ARIE occurred in 20 (48.8%) of 41 patients: seven in the glutamine-supplemented group, and 13 in the glutamine-free group (p=0.002). All seven patients with grade 3 esophagitis were in the glutamine-free group (36.8% vs. 0%). Glutamine supplementation appeared to significantly delay ARIE onset for six days (22 days vs. 16 days; p=0.002). Glutamine-supplemented patients demonstrated a lower incidence of grade 2 or 3 ARIE (27.2%), and gained weight during radiotherapy (p=0.04). V55 was the only dosimetric parameter that correlated with the severity of ARIE in glutamine-free patients: a V55 of <35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 of >or=35% (p=0.01). CONCLUSION: This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients.

BACKGROUND: Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients. METHODS: Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m2) and docetaxel (80 mg/m2); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol. RESULTS: Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage. CONCLUSION: The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.

Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury.

PURPOSE: We compared the effects of amifostine and melatonin in preventing radiation-induced epiphyseal growth plate injury in rats. MATERIALS AND METHODS: Four-week-old (65-85 g), growing male Sprague-Dawley rats were randomly assigned to receive radiation alone, at 25 Gy in three fractions (group R), or this dose of fractionated radiation proceeded by prophylactic amifostine 200 mg/kg i.p. (group A), melatonin 15 mg/kg i.p. (group M), or amifostine + melatonin (group AM). The right rear extremity of each animal was irradiated while the contralateral leg was shielded from radiation, as a control. Bone growth based on the length of the tibia, femur, and overall limb was calculated 6 weeks after the treatment. RESULTS: In groups R, A, M, and AM, the mean growth loss (GL) for the overall limb was 56.9 +/- 8.1%, 46.8 +/- 7.7%, 36.6 +/- 4.3%, and 38.5 +/- 5.1%, respectively. The limb length discrepancies (LLD) in groups R, A, M, and AM were 13.8 +/- 1.4%, 10.5 +/- 0.3%, 7.4 +/- 0.7%, and 8.8 +/- 1.1%, respectively. Differences in LLD were significant between each treatment group and group R (range: p = 0.0001-0.001). Differences in either of mean GL and LLD were not significant between groups M and AM; however both of these groups had significantly less GL and LLD than group A. CONCLUSIONS: We observed a superior radioprotective function of melatonin over amifostine in preventing radiation-induced epiphyseal growth plate injury, without any increase in radioprotective effect by adding amifostine to melatonin.

Managing liver metastases with conformal radiation therapy.

A subgroup of liver metastases, especially those emanating from colorectal carcinoma, may be cured. Surgical excision is accepted as the mainstay of treatment for these malignancies; unfortunately, however, the majority of patients presents with advanced unresectable hepatic involvement and have no standard treatment option available. Radiation therapy (RT) has not played a significant role in managing liver metastases, because the liver has little tolerance to radiation. In patients with good hepatic function, however, very-high-dose RT may be used safely and effectively if a small volume of the liver (< 25%) is irradiated. In particular, RT, and especially three-dimensional conformal RT (3D-CRT), may be used to manage medically unfit patients or those with an unresectable metastatic liver lesion. This review discusses existing literature on use of various types of RT, including whole-liver irradiation, partial hepatic irradiation with 3D-CRT, and hypofractionated high-dose irradiation with stereotactic body RT, and future directions for this treatment modality.

Primary cerebral neuroblastoma: a case treated with adjuvant chemotherapy and radiotherapy.

Neuroblastoma is the most common extracranial solid tumor of childhood. A wide variety of tumor locations and clinical presentations have been described. However, neuroblastoma is rarely located in the central nervous system, except in the case of esthesioneuroblastoma. We report a child with primary central nervous system (CNS) neuroblastoma who admitted to the hospital in coma. The tumor could be partially removed in our patient. After surgery, we treated the patient successfully with combined radiotherapy and eight courses of cisplatin-based chemotherapy. Our patient was followed-up for 34 months without any evidence of relapse.

Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma.

Cytokines play important roles in the pathogenesis of lymphomas. The aim of this study was to determine the relations between serum levels of interleukin-2 (IL-2), IL-6, and IL-10 and parameters of International Prognostic Index (IPI). Serum levels of IL-2, IL-6, and IL-10 were measured using a sensitive enzyme-linked immunosorbent assay in the pretreatment frozen sera from 43 patients with non-Hodgkin's lymphoma. The patients we included in the study were divided into two groups, one with high risk and the other with low risk according to the IPI in regard to their ages, stages, performance status, extranodal involvements, and serum levels of lactate dehydrogenase. In the high-risk group, serum levels of IL-2 (0.852 +/- 0.268 ng/ml), IL-6 (0.461 +/- 0.206 ng/ml), and IL-10 (0.816 +/- 0.240 ng/ml) were found to be higher than serum levels of IL-2 (0.667 +/- 0.170 ng/ml), IL-6 (0.355 +/- 0.075 ng/ml), and IL-10 (0.643+0.177 ng/ml) in the low-risk group ( < 0.05). There was a correlation between the patients with high risk according to the IPI criteria and high levels of serum cytokines (IL-2, IL-6, IL-10). Knowledge of the serum levels of these cytokines in patients with newly diagnosed aggressive non-Hodgkin's lymphoma may help us to have some information about the possible prognosis, the activation of disease, and to decide on appropriate therapeutic approaches for individual patients.