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At least 91 records · Page 5Linked to original sources

Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy.

AIM: To evaluate the use of scatter laser photocoagulation to prevent radiation related retinopathy, maculopathy, and loss of vision. METHODS: This was an interventional case series. 66 eyes with posterior choroidal melanomas treated by ophthalmic plaque radiation therapy were reported. Of these patients, 50 were selected because they developed radiation retinopathy; 45 of these were treated with sector scatter laser photocoagulation to regress clinically evident radiation retinopathy. 16 additional patients (considered to be "high risk" to develop radiation retinopathy) were also treated. RESULTS: Radiation retinopathy was noted to appear at a mean interval of 26 months following plaque treatment. Laser photocoagulation regressed radiation retinopathy in 29 (64.4%) of the 45 patients treated after the onset of radiation retinopathy (17 with only retinopathy, 10 with a combination of retinopathy and maculopathy, and two with only maculopathy). Of the 16 patients who received laser treatment before clinical evidence of retinopathy, one developed radiation maculopathy and two retinopathy without maculopathy (all three responded to additional laser photocoagulation). In the 45 patient group, vision loss of more than three lines was attributable to radiation maculopathy in seven (15.5%). None of the patients in the prophylactic laser group lost more than three lines of vision as a result of maculopathy. CONCLUSION: Sector scatter argon laser photocoagulation induced regression of radiation retinopathy. Though early treatment of radiation retinopathy appears to be more effective, a more long term and prospective randomised study will be needed to prove efficacy.

Adult↗

Interaction between radiation and drug damage in mammalian cells. VI. Radiation and doxorubicin age-response function of doxorubicin-sensitive and -resistant Chinese hamster cells.

A comparative study of the radiation and/or doxorubicin (DOX) survival response for synchronous populations of Chinese hamster V79 cells and two DOX-resistant variants (77A and LZ-8) was performed. The greatest cellular radiation sensitivity was observed in mitosis, while the greatest resistance was observed during late S phase for the three cell lines. The variation in radiation response throughout the cell cycle was expressed as a change in the width of the shoulder of the survival curves (Dq) with little change in D0. This suggests that each phase of the cell cycle has a different capacity for accumulation of radiation injury. The radiation age-response function for the three cell lines revealed that 77A and LZ-8 cells were more radiosensitive than V79 cells throughout the cell cycle. Exposure of synchronous populations to DOX (1.84 microM for V79, 9.21 microM for 77A, and 921 microM for LZ-8) for 1 h as a function of cell cycle phase revealed that V79, 77A, and LZ-8 cells exhibited the greatest sensitivity to DOX in mitosis and the most resistance to DOX during S phase, as indicated by the differences in the slope of the initial component of the survival curve. Levels of P-glyco-protein (P-gp) are probably not a factor contributing to DOX age-response function since P-gp levels remain constant throughout the cell cycle in all three cell lines. Synchronous populations of V79, 77A, and LZ-8 cells sequentially treated with DOX and radiation at various cell cycle phases were also analyzed. The results showed that the interaction between radiation and DOX damage resulted in a reduced cellular capacity for the accumulation of radiation damage throughout the cell cycle, as indicated by a decrease in the width of the shoulder of the survival curve. Overall, both DOX-sensitive V79 cells and DOX-resistant 77A and LZ-8 cells exhibited (1) a similar age-response function for radiation or DOX, and (2) no differences in the effects of DOX on radiation-induced damage throughout the cell cycle. These results indicate that acquired resistance to DOX associated with increased levels of P-gp in the cell membrane did not appear to affect the age-response function for radiation or DOX, and the nature of the interaction between damage caused by radiation and DOX was also not affected.

Animals↗

Clinical radiation pneumonitis and radiographic changes after thoracic radiation therapy for lung carcinoma.

BACKGROUND: The authors attempted to determine the incidence of and risk factors for clinical radiation pneumonitis in patients treated for lung carcinoma. They also sought to describe the corresponding posttreatment radiographic changes. METHODS: Between 1989-1993, 83 patients received curative radiation therapy for lung carcinoma. Of these, 39 patients were treated with definitive radiation therapy, and 44 patients were treated with adjuvant radiation therapy after surgical resection. The median radiation therapy dose was 54 gray (Gy), and the median treatment area was 182 cm2. Chest radiographs obtained after radiation therapy were reviewed and scored for margin definition, volume loss, and texture quality. RESULTS: A total of 17 patients (20%) developed clinical radiation pneumonitis (CRP). The median radiation therapy dose for the CRP cohort was 54 Gy, and the median treatment volume was 193 cm2. The median time to onset of symptoms was 3 weeks after radiation therapy, and the median duration of symptoms was 10 weeks. Of the 15 evaluable patients, symptoms resolved for 9 patients, improved but persisted for 4 patients, and CRP was fatal for 2 patients. The incidence of CRP was increased for patients with low performance status, comorbid lung disease, smoking history, low pulmonary function tests, and for those patients who did not undergo a surgical resection. Posttreatment radiographic changes were common and progressed with time. Radiographic changes were more pronounced in the CRP cohort, and extended outside the radiation therapy treatment field in the majority of patients (67%). CONCLUSIONS: Clinical radiation pneumonitis developed in 20% of lung carcinoma patients. Risk factors included low performance status, comorbid lung disease, smoking history, low pulmonary function tests, and the absence of a surgical resection. Posttreatment radiograph changes were common and progressed with time, and typically were not confined to the radiation therapy treatment field.

Adult↗

Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001.

Exposures to doses of radiation of 1-10 Gy, defined in this workshop as moderate-dose radiation, may occur during the course of radiation therapy or as the result of radiation accidents or nuclear/radiological terrorism alone or in conjunction with bioterrorism. The resulting radiation injuries would be due to a series of molecular, cellular, tissue and whole-animal processes. To address the status of research on these issues, a broad-based workshop was convened. The specific recommendations were: (1) RESEARCH: Identify the key molecular, cellular and tissue pathways that lead from the initial molecular lesions to immediate and delayed injury. The latter is a chronic progressive process for which postexposure treatment may be possible. (2) Technology: Develop high-throughput technology for studying gene, protein and other biochemical expression after radiation exposure, and cytogenetic markers of radiation exposure employing rapid and accurate techniques for analyzing multiple samples. (3) Treatment strategies: Identify additional biological targets and develop effective treatments for radiation injury. (4) Ensuring sufficient expertise: Recruit and train investigators from such fields as radiation biology, cancer biology, molecular biology, cellular biology and wound healing, and encourage collaboration on interdisciplinary research on the mechanisms and treatment of radiation injury. Communicate knowledge of the effects of radiation exposure to the general public and to investigators, policy makers and agencies involved in response to nuclear accidents/events and protection/treatment of the general public.

Animals↗

The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation.

PURPOSE: To determine the impact of postoperative radiation on locoregional relapse and overall survival rate in a multimodality protocol for locally advanced breast cancer (LABC). MATERIAL AND METHODS: Of the patients entered in the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response had been achieved; modified radical mastectomy; 6 courses of postoperative adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate analysis of locoregional response and overall survival was done. RESULTS: Of the total, 42 patients received chest wall radiation; 28 of these also received radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy to the whole chest wall, with 31 patients receiving an additional chest-wall boost. The incidence of locoregional relapse with and without radiation was 7% vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those receiving radiation, with a mean overall survival of 50 months vs. 20 months, and a 3-year overall survival of 88% vs. 46% with and without radiation, respectively (p = 0.003). Multivariate analysis showed that overall survival was affected by the presence of pathological CR (p = .047), the number of pre-operative chemotherapy cycles (p = .036) and whether or not they received radiation (p = 0.003). Neither the interval between surgery and radiation, technique of radiation, nor radiation modality significantly affected local control. CONCLUSION: The significant improvement in local regional control and overall survival with the addition of radiation suggests that radiation should be an integral part of multimodality management of locally advanced breast cancer.

Adult↗

Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.

Radiation-induced biochemical events that mediate the intracellular signal transduction leading to cell apoptosis are largely unknown. Limited evidence suggests the possible involvement of one or more protein-tyrosine kinases (PTKs) in radiation-induced cellular responses, including apoptosis. However, so far, a PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular substrates has not been identified and the role of the PTK(s) in the radiation-induced apoptosis remains unclear. To examine the roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells following radiation. When DT40 B cells were exposed to radiation, the activity of Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15 s), and then decreased, whereas Lyn kinase activity increased and reached a maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn-deficient DT40 B cells. These results indicate that Syk and Lyn kinases are involved in radiation-induced signal transduction, with different kinetics. In addition, our results revealed that functional inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested that the activation of Syk or Lyn kinase alone may be sufficient to mediate the radiation-induced apoptosis in DT40 B cells, or both kinases may not be required for this biological process.

Animals↗

Elapsed radiation therapy treatment time as a predictor of survival in patients with advanced head and neck cancer who receive chemotherapy and radiation therapy.

PURPOSE: To determine whether elapsed radiation therapy treatment time relates to survival in patients with head and neck cancer treated sequentially with chemotherapy and radiation therapy. MATERIALS AND METHODS: From 1981 to 1988, 76 adult patients with bulky stage II-IV head and neck cancer received induction chemotherapy (fluorouracil and cisplatin). Those with a complete or partial response (n = 46) received full-dose definitive radiation therapy (range, 64.0-77.5 Gy; median, 70 Gy). Those with less than a partial response (n = 21) underwent surgery and postoperative radiation therapy (n = 15), palliative radiation therapy (n = 4), or palliative chemotherapy (n = 2). Nine patients refused to undergo radiation therapy after induction chemotherapy. RESULTS: The 5-year overall survival rates were as follows: 32% in all patients, 38% in patients who underwent chemotherapy and radiation therapy, and 27% in patients who underwent chemotherapy, surgery, and radiation therapy. The number of days between radiation therapy treatments was highly predictive of overall survival. In the groups with treatments less than 55 days apart, 56-65 days apart, and more than 66 days apart, the 5-year survival rates were 56%, 46%, and 15%, respectively (P = .02). CONCLUSION: The time between radiation therapy treatments is strongly predictive of survival in patients undergoing sequential chemotherapy and radiation therapy. The use of induction chemotherapy does not negate the need to avoid treatment interruptions during definitive radiation therapy.

Adult↗

Radiation-induced lung disease and the impact of radiation methods on imaging features.

Although radiologic findings in radiation-induced lung disease are well described in the literature, the influence exerted on these findings by different radiation methods is not well understood. Radiation treatment of non-small cell lung cancer varies depending on the location and extent of disease. Irradiation with oblique beam angles results in unusual distribution of radiation-induced lung disease. Small cell lung cancer is treated with irradiation concurrent with or following chemotherapy, and portal arrangements are controversial. In breast cancer, use of tangential beam portals may induce radiation pneumonitis or fibrosis at the peripheral lung anterolaterally. Use of supraclavicular portals may produce lesions in the lung apex that appear similar to pulmonary tuberculosis. In esophageal cancer, radiation portals with a 5-6-cm margin above and below the tumor are generally recommended, and computed tomography (CT) frequently demonstrates radiation-related lung damage adjacent to the mediastinum. In mediastinal tumors, the mantle field includes all the major lymph node regions above the diaphragm. Radiation pneumonitis varies from minimal to extremely marked change in the paramediastinal areas and in both apices. CT is more sensitive to radiation-induced lung disease than chest radiography and demonstrates related changes earlier. Furthermore, it more clearly depicts the precise distribution and pattern of disease. Familiarity with the imaging findings in radiation-induced lung disease produced by different radiation methods will help radiologists interpret abnormalities seen at chest radiography and CT in affected patients.

Breast Neoplasms↗

Paradigm shifts in radiation biology: their impact on intervention for radiation-induced disease.

New mechanistic cell and molecular studies on the effects of very low doses of radiation have resulted in three major paradigm shifts. First, the observation of bystander effects demonstrated that non-hit cells may respond as well as cells in which energy is deposited. Second, it was thought that gene mutations and chromosome aberrations were the most important early changes that represented the initiation phase of radiation-induced cancer. Now genomic instability that leads to the loss of genetic control appears to play a major role in the development of cancer. Finally, recent studies have demonstrated that radiation-induced changes in gene expression can be demonstrated at very low radiation doses. These changes can result in alterations in response pathways, many of which appear to be involved in protective or adaptive responses. The demonstration that unique genes are up- and down-regulated depending on the radiation type, dose and dose rate suggests that different molecular mechanisms are involved in responses to high and low radiation doses. The ability to alter radiation response by physical and chemical treatments suggests that it may be possible to intervene in the progression of radiation-induced diseases. Such intervention may decrease the cancer risk from radiation exposure. This new research also demonstrates that many nonlinear biological processes have an impact on the induction of cancer and the shape of dose-response functions. Thus, for low-LET radiation delivered at low dose rates, the linear, no-threshold hypothesis is not well supported, but it is adequately conservative in protecting against low-dose radiation risks.

Adaptation, Physiological↗

Low level X-radiation effects on carcinogenesis by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium: acute vs fractionated radiation dose studies.

Studies examined the effects of acute and fractionated low to moderate level X-ray exposures on hamster cheek pouch carcinogenesis in vivo by 7,12-dimethylbenz(a)anthracene (DMBA). Animals were grouped by treatment as follows: acute doses of 0.85-3.40 Gy X rays; 17 once weekly doses of 0.01-0.20 Gy X rays (fractionated radiation); topical DMBA for 10 weeks; DMBA plus fractionated radiation starting together; DMBA plus acute radiation in Week 1 or 10 of DMBA treatments; and sham irradiation, DMBA vehicle, or anesthesia controls. After 44 weeks, hamsters were sacrificed, and their cheek pouches were excised, serially sectioned, and examined by light microscopy for histopathology. No histologic changes were observed in radiation-only hamsters. Carcinoma incidences in DMBA-only groups ranged from 45 to 60%. Carcinoma incidences were greater in groups receiving DMBA plus fractionated radiation than in groups receiving either acute radiation + DMBA or DMBA alone. Carcinoma incidences in acute radiation plus DMBA groups were lower than those in DMBA-only groups. These results suggest complex interactions between radiation and DMBA, perhaps with radiogenic cell killing being a principal factor in acute radiation + DMBA groups, and reciprocal additive or synergistic effects of radiation and DMBA on cancer induction and manifestation in fractionated radiation + DMBA groups.

9,10-Dimethyl-1,2-benzanthracene↗

Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma patients: the potential for increased radiation toxicity.

PURPOSE: Surgically resected melanoma patients with high-risk features commonly receive adjuvant therapy with interferon-alpha 2b combined with radiation therapy; the purpose of our study was to evaluate the potential enhancement of radiation toxicity by interferon. METHODS AND MATERIALS: Patients at LDS Hospital and the University of Utah Medical Center in Salt Lake City treated with interferon during radiotherapy or within 1 month of its completion were retrospectively identified, and their charts were reviewed. If possible, the patients were asked to return to the LDS Hospital radiation therapy department for follow-up. RESULTS: Five of 10 patients receiving interferon-alpha 2b therapy during radiation therapy or within 1 month of its completion experienced severe subacute/late complications of therapy. Severe subacute/late complications included two patients with peripheral neuropathy, one patient with radiation necrosis in the brain, and two patients with radiation necrosis in the s.c. tissue. One patient with peripheral neuropathy and one patient with radiation necrosis also developed lymphedema. CONCLUSIONS: In vitro studies have identified a radiosensitizing effect by interferon-alpha on certain cell lines, which suggests the possibility that patients treated with interferon and radiation therapy may experience more severe radiation toxicities. We have observed severe subacute/late complications in five of 10 patients treated with interferon-alpha 2b during radiation therapy or within 1 month of its completion. Although an observational study of 10 patients lacks the statistic power to reach conclusions regarding the safety and complication rates of combined interferon and radiation therapy, it is sufficient to raise concerns and suggest the need for prospective studies.

Adult↗

Single dose radiation is more effective for the UV-induced activation and proliferation of melanocytes than fractionated dose radiation.

PURPOSE: To establish whether the effect of fractionating radiation modifies the effects of ultraviolet (UV) radiation on epidermal melanocytes, we compared the clinical and histological effects of single high dose radiation against repeated intermediate to low dose radiation on epidermal melanocytes. METHODS: Three minimal erythema UV doses (MED) were administered to three sites on the buttocks of healthy volunteers. One site was irradiated with 0.5 MED UV every day for 6 consecutive days, another site was irradiated with 1 MED UV every second day, and a third site received a single dose of radiation with 3 MED UV. The treatment was replicated on the other buttock. For the evaluation of UV-induced erythema and pigmentation, erythema and melanin indices were measured at 2 and 14 days post-irradiation. For purposes of histological evaluation, tissue specimens taken from each irradiated site at 2 and 14 days post-irradiation and were stained with monoclonal antibodies against Mel-5, HMB-45 and tyrosinase. Fontana-Masson silver staining, DOPA staining and split DOPA reactions were also performed. RESULTS: At 14 days post-irradiation, UV radiation induced melanocyte activation, proliferation and melanogenesis in proportion to the radiation dose administered to each fraction. The most prominent responses were observed after single high doses of radiation. CONCLUSION: When the total administered dose is identical, fractionation of radiation dose diminishes the effects of UV radiation on epidermal melanocytes. Furthermore, long, uninterrupted doses of UV radiation were found to more effective in inducing melanogenesis and melanocyte activation.

Adult↗