Systematic review of amifostine for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. RESULTS: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. CONCLUSION: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. MATERIALS AND METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for use of each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. RESULTS: Forty-one papers were reviewed. There was sufficient evidence to recommend the use of benzydamine mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving moderate-dose radiation therapy (up to 50 Gy), without concomitant chemotherapy. A new suggestion was developed against the use of misoprostol mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving radiation therapy. Positive results were reported for some other anti-inflammatory agents. However, no guidelines were able to be developed for any other agents due to insufficient and/or conflicting evidence. CONCLUSIONS: The use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. Additional well-designed studies are needed to examine the use of this class of agents for oral mucositis.

Liposomal doxorubicin in conjunction with reirradiation and local hyperthermia treatment in recurrent breast cancer: a phase I/II trial.

PURPOSE: This is the first study to evaluate the tolerability and activity of liposomal doxorubicin (Caelyx; Schering-Plough Pharmaceuticals) < or =60 mg/km(2) in patients with locally recurrent breast cancer, when administered in conjunction with reirradiation and local hyperthermia treatment. EXPERIMENTAL DESIGN: Fifteen female patients, who had undergone a radical mastectomy and conventional radiotherapy (60 Gy) in the front chest wall, were entered on a multimodal protocol consisting of initial treatment with radiotherapy and a monthly infusion of liposomal doxorubicin < or =60 mg/m(2) in conjunction with local hyperthermia treatment. All patients received reirradiation up to a total dose of 30.6 Gy (1.8 Gy/fraction, 5 days a week). To evaluate the drug's safety, the first 5 patients initially received a dose of 40 mg/m(2) liposomal doxorubicin, which was then escalated to 60 mg/m(2). The other 10 patients received 60 mg/m(2) for all six cycles of chemotherapy. Hyperthermia (HT) was produced in the region of interest (ROI) using waveguides at a frequency of 433 MHz. The RSS was obtained from the curves representing the change in the ROI's surface with time for each patient, as fitted by linear regression. Linear regression analysis was used to study the relationship between the time interval from liposomal doxorubicin infusion to HT and the RSS. RESULTS: At doses of < or =60 mg/m(2), liposomal doxorubicin was well tolerated, with only mild hematological and nonhematological toxicity. All patients showed an objective measurable response, with 3 patients (20%) demonstrating a clinically complete response. There was a significant correlation between the duration of response and Avg Min T(90) > 44 degrees C (r(s) = 0.917, P < 0.0001) and the Mean[Tmin] (r(s) = 0.909, P < 0.0001). The RSS was significantly correlated with the interval between liposomal doxorubicin infusion and HT, as the smaller the time interval, the greater the clinical benefit (r = 0.76, P = 0.001). CONCLUSIONS: The multimodal treatment was effective and well tolerated, producing an objective measurable response in all patients. Local HT had a significant effect on patients' response to the drug. The relationship between thermal dose and liposomal action requires further investigation.

Impact on cytoprotective efficacy of intermediate interval between amifostine administration and radiotherapy: a retrospective analysis.

PURPOSE: To evaluate the cytoprotective impact of the interval between amifostine administration and radiotherapy (RT). METHODS AND MATERIALS: In a nonrandomized study, we reviewed the records of 177 patients with tumors localized in the pelvis (prostate, bladder, or gynecologic cancer), upper abdomen (pancreas, stomach, kidney), thorax (lung and breast cancer), head and neck (nasopharynx), soft tissue (sarcomas), and central nervous system. The patient records were stratified according to whether the patients had undergone RT either 25-40 min (Group 1, 96 subjects) or 10-15 min (Group 2, 81 subjects) after i.v. amifostine administration. The mean toxicity score was the mean value of recorded acute radiation toxicity. The mean interruption time was the mean value of the recorded interruption time due to radiation toxicity. RESULTS: A significantly reduced severity of symptoms related to oral (p = 0.023), esophageal (p = 0.05) and rectal (p = 0.015) mucosa was noted in Group 2. A statistically significant reduction in the mean toxicity score (p <0.001) and mean interruption time (p = 0.001) was observed in Group 2 vs. Group 1. In terms of the incidence of radiation-induced dermatitis and alopecia, multivariate logistic analysis revealed only the total dose (p = 0.018) and the amifostine-RT interval (p = 0.002) as independent factors. CONCLUSION: A significantly better cytoprotective effect of amifostine against radiation-induced mucositis, dermatitis, and alopecia was noted if RT was administered no later than 15 min after i.v. amifostine infusion. The results presented here need additional investigation with randomized prospective trials.

CT-MRI automatic surface-based registration schemes combining global and local optimization techniques.

Medical image registration is commonly required in order to combine the complementary information provided by different medical imaging modalities. In this paper, a new automatic registration scheme is proposed to register 3-D CT-MR head images and is currently tested on a clinical environment. The proposed scheme, after the preprocessing and the outer surface extraction of the data, is based on the use the rigid transformation method, in conjunction with a combination of global and local optimization techniques. Analytically, the paper exploits the optimization efficiency of three widely used optimization techniques, in obtaining the parameters of the rigid transformation model: the Downhill Simplex Method, the Genetic Algorithms and the Simulated Annealing. These optimization techniques are further combined by the sequential application of the Powell optimization method in order to refine the registration and increase its accuracy. A comparative study involving these optimization techniques in conjunction with the rigid transformation, and two other methods, the ICP and the manual methods, is also presented, for a sufficient number of clinical CT-MR brain images. Finally, quantitative and qualitative results are also presented to validate the performance of these automatic surface-based registration schemes, in terms of consistency and accuracy. Throughout of this study, the automatic registration scheme comprising of the rigid transformation in conjunction with the Simulated Annealing method sequentially combined with the Powell method has been performed superior regarding all the other compared registration schemes.

Physical activity and mammographic parenchymal patterns among Greek postmenopausal women.

OBJECTIVE: To examine whether physical activity during the last five years is related to later breast mammographic density in postmenopausal Greek women. METHODS: We designed a cross-sectional study in 724 women, of ages 45-67 years. An interview-administered questionnaire was used to obtain information on duration and intensity of recreational physical activity during five years preceding study recruitment. Mammograms were evaluated according to BIRADS classification and BIRADS score was also estimated. Multivariate ordinal logistic regression analysis was used to assess associations between physical activity index and breast density according to the BIRADS classification methods. RESULTS: We observed a statistically significant inverse association of mammographic breast density measured by the BIRADS classification method and recreational exercise (OR=-0.10; 95% CI -0.018, -0.001; p=0.022). For one unit increase in physical activity as expressed by the MET-h/week score, the odds of lower versus higher breast density categories are 1.105 greater, given that all of the other variables in the model are held constant. A modifying effect by age at recruitment was evident among participants, with a stronger inverse association between recreational activity and mammographic breast density among older women (OR=-0.036; 95% CI -0.063, -0.009; p=0.009). An inverse association between physical activity and BIRADS score was evident, not reaching statistical significance (OR=0.00; 95% CI -0.009, 0.008; p=0.887). CONCLUSIONS: Mammographic breast area was lower in postmenopausal women who participated in sports/recreational physical activity compared to inactive controls. Increasing physical activity levels among postmenopausal women might be a reasonable approach to reduce mammographic density. However, until more physical activity and mammographic breast density studies are conducted that confirm our findings, they have to be interpreted with caution, due to the retrospective nature of our data and the possibility of memory bias.

Therapeutics interventions with anti-inflammatory creams in post radiation acute skin reactions: a systematic review of most important clinical trials.

The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.

Use of image processing techniques to assess effect of disodium pamidronate in conjunction with radiotherapy in patients with bone metastases.

The aim of this study was radiographically to monitor the effect of disodium pamidronate on metastatic bone disease, using image-processing techniques. Eighteen patients with osteolytic metastases from breast cancer received an intravenous infusion of 180 mg disodium pamidronate every 4 weeks for a period of 6 months. The first session of intravenous infusions was given concurrently with external beam radiotherapy with a 6 MV linear accelerator (total dose 30 Gy in 10 fractions). Radiographs of osteolytic lesions were obtained at every session of the treatment, retaining the same settings for each modality. The analysis of the attributes of the images was based on measuring the first-order statistics of the gray-level histogram in terms of mean value (MVGLH) and energy (EGLH). The measurements showed significant differences for MVGLH and EGLH values (p < 0.05, Wilcoxon test). Analytically, there was an 11.08% (95% CI = 10.21, 11.93) mean reduction of EGLH and an 11.63% (95% CI = 10.96, 12.29) mean increase of MVGLH of the x-ray images, before and after the combined treatment protocol. The changes in the image-processing indices were also highly correlated with the reduction of the patient's pain score. These findings indicate an important increase in bone mass and bone formation, which the radiologists found difficult to identify visually.