Genetic and teratogenic effects of cancer treatments on gametes and embryos.
(73/1791)
Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring. (+info)
Solid-tumor mortality in the vicinity of uranium cycle facilities and nuclear power plants in Spain.
(74/1791)
To ascertain solid tumor mortality in towns near Spain's four nuclear power plants and four nuclear fuel facilities from 1975 to 1993, we conducted a mortality study based on 12,245 cancer deaths in 283 towns situated within a 30-km radius of the above installations. As nonexposed areas, we used 275 towns lying within a 50- to 100-km radius of each installation, matched by population size and sociodemographic characteristics (income level, proportion of active population engaged in farming, proportion of unemployed, percentage of illiteracy, and province). Using log-linear models, we examined relative risk for each area and trends in risk with increasing proximity to an installation. The results reveal a pattern of solid-tumor mortality in the vicinity of uranium cycle facilities, basically characterized by excess lung [relative risk (RR) 1.12, 95% confidence interval (CI), 1.02-1.25] and renal cancer mortality (RR 1.37, 95% CI, 1.07-1.76). Besides the effects of natural radiation, these results could well be evincing the influence on public health exerted by the environmental impact of mining. No such well-defined pattern appeared in the vicinity of nuclear power plants. Monitoring of cancer incidence and mortality is recommended in areas surrounding nuclear fuel facilities and nuclear power plants, and more specific studies are called for in areas adjacent to installations that have been fully operational for longer periods. In this regard, it is important to use dosimetric information in all future studies. (+info)
Quantification of the ultraviolet radiation (UVR) field in the human eye in vivo using novel instrumentation and the potential benefits of UVR blocking hydrogel contact lens.
(75/1791)
BACKGROUND/AIMS: Certain degenerative eye conditions occur predominantly nasally, at the limbal region, and are associated with solar ultraviolet radiation (UVR) induced damage. The relative contribution to the in vivo ocular flux of (a) the reflection of UVR incident on the skin of the nose onto the nasal limbus, and (b) the focusing of UVR incident on the temporal side of the cornea onto the nasal limbus were examined. METHODS: A novel photodiode sensor array was used to measure the UVR field across the eye. In addition, a novel spectrometer set-up was used to measure the spectrum of radiation refracted across the cornea. The efficacy of UVR blocking hydrogel contact lenses in filtering incident UVR was assessed in vivo. RESULTS: Qualitative and quantitative data indicated an increase nasally of UVR. Photodiode readings showed a net UVR increase from the temporal to the nasal side. Transmission curves showed that most UVR incident on the limbal region is either absorbed by, or transmitted through, the ocular tissues. This radiation is filtered by UVR blocking soft contact lens. CONCLUSIONS: An increased UVR flux on the nasal side of the eye, due to reflection off the nasal skin, was identified in vivo. Any UVR passing through the cornea is either absorbed by the conjunctiva and/or transmitted through it onto the sclera where it is absorbed. UVR blocking hydrogel contact lenses can eliminate these sources of UVR. (+info)
Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.
(76/1791)
PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy. (+info)
Medulloblastoma: clinical and biologic aspects.
(77/1791)
Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. The biologic underpinnings of medulloblastoma are not fully characterized, but recent work has identified new, important directions for research. Stratification of patients with medulloblastoma into risk groups is the backbone of most ongoing therapeutic studies. Patients are usually characterized as being either average risk or poor risk, although an intermediate risk group may exist. Standard treatment for older children with medulloblastoma consists of radiation and, for most, chemotherapy. Children with nondisseminated disease at the time of diagnosis have been reported to have as high as an 80% five-year disease-free survival rate after treatment with reduced dose (2340 cGy) craniospinal irradiation, local boost radiation therapy (5500 cGy), and chemotherapy, given during and after radiation therapy. Preradiation chemotherapy has yet to be shown to be of benefit for children with medulloblastoma. Children with disseminated disease are a highly problematic subgroup of patients to treat. A variety of new approaches are being studied, most of which are intensifying chemotherapy either prior to or after radiation. Long-term survivors of medulloblastoma are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae. Infants and very young children with medulloblastoma remain a difficult therapeutic challenge because they have the most virulent form of the disease and are at highest risk for treatment-related sequelae. (+info)
Brain tumors in children with neurofibromatosis: additional neuropsychological morbidity?
(78/1791)
Neurofibromatosis type 1 is a common autosomal dominant genetic disorder associated with numerous physical anomalies and an increased incidence of neuropsychological impairment. Tumors of the CNS occur in approximately 15% of children with neurofibromatosis, presenting additional risk for cognitive impairment. This study examines the impact of an additional diagnosis of brain tumor on the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological tests was administered to 149 children with neurofibromatosis. Thirty-six of these children had a codiagnosis of brain tumor. A subset of 36 children with neurofibromatosis alone was matched with the group of children diagnosed with neurofibromatosis and brain tumor. Although mean scores of the neurofibromatosis plus brain tumor group were, in general, lower than those of the neurofibromatosis alone group, these differences were not statistically significant. Children in the neurofibromatosis plus brain tumor group who received cranial irradiation (n = 9) demonstrated weaker academic abilities than did children with brain tumor who had not received that treatment. These results suggest that neurofibromatosis is associated with impairments in cognitive functioning, but the severity of the problems is not significantly exacerbated by the codiagnosis of a brain tumor unless treatment includes cranial irradiation. (+info)
Review article: current therapeutic options for radiation proctopathy.
(79/1791)
Radiation proctopathy is a common unfortunate complication following radiation therapy of pelvic malignancies. Symptoms of chronic radiation proctopathy include haematochezia, urgency, constipation, tenesmus, diarrhoea and rectal pain. Currently, a wide variety of pharmacological options, endoscopic cautery techniques and surgical procedures have been proposed for the treatment of chronic radiation proctopathy. Although these have been proposed primarily as treatment for rectal bleeding, the control of other symptoms has been noted with some of these agents. Pharmacological options include 5-aminosalicylic acid preparations, coticosteroid enemas, sucralfate (oral, enemas), formalin, short chain fatty acid enemas, oestrogen/progesterone, hyperbaric oxygen, antioxidants, sodium pentosan polysulphate and misoprostol rectal suppositories. Of these, sucralfate and formalin therapy appear to be effective for bleeding control. Misoprostol rectal suppositories and oral sucralfate may be useful in the prevention of acute and chronic symptoms of radiation proctopathy. Endoscopic cautery techniques have included the use of Nd:YAG laser and argon laser for coagulation of bleeding neovascular telangiectasias. Argon plasma coagulation offers a safe non-contact method of delivering haemostasis which has proven to be particularly useful in targeting difficult to reach lesions tangentially. Surgery is generally reserved for severe refractory cases involving ongoing haemorrhage, obstruction, stricture formation, fistulas and perforation. Given that formal randomized placebo-controlled studies are lacking for most treatments, the management of these patients is often challenging and unclear. Hence, there is a need for more research and education on radiation proctopathy. (+info)
The consequences of treatment and disease in patients with primary CNS non-Hodgkin's lymphoma: cognitive function and performance status. North Central Cancer Treatment Group.
(80/1791)
Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome. (+info)