Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer

BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.     

Immune modulation with interleukin-4 and interleukin-10 prevents crescent formation and glomerular injury in experimental glomerulonephritis

Crescentic glomerulonephritis (GN) demonstrates immunopathological features of a T helper (Th)1-directed delayed-type hypersensitivity (DTH) response. The capacity of Th2 cytokines to attenuate crescentic glomerular injury in this disease was examined by administering interleukin (IL)-4 and IL-10, singly and in combination. GN was induced by i.v. administration of sheep anti-mouse glomerular basement membrane (GBM) globulin to mice sensitized to sheep globulin 10 days earlier. Treatment (2.5 μg, i.p.) with IL-4, IL-10, or both IL-4 and IL-10 (IL-4+10), was started 1 h before sensitization and continued daily until the end of the study (10 days after administration of anti-GBM globulin). Control mice treated with PBS developed GN with glomerular accumulation of T cells and macrophages, crescents in 42.5 ± 4.5 % of glomeruli (normal 0 %), proteinuria (8.3 ± 0.9 mg/24 h, normal 0.74 ± 0.08 mg/24 h, p < 0.001) and renal impairment (creatinine clearance [cr/cl]: 93 ± 12 μ1/min, normal 193 ± 10 μ1/min, p<0.001). 1reatment with either IL-4, IL-10, or IL-4+10 prevented crescent formation (crescentic glomeruli: 0.8 ± 0.5, 1.2 ± 0.9, and 1.4 ± 1.0 %, respectively, all p<0.01 compared to control) and attenuated proteinuria (3.6 ± 1.0, 2.2 ± 0.5, and 2.9 ± 0.5 mg/24 h, respectively, all p<0.01 compared to control). IL-4+10 prevented development of renal impairment (cr/cl: 183 ± 22 μ1/min); IL-10 given alone limited the decline in renal function (cr/cl: 150 ± 20 μ1/min), but IL-4 alone did not provide any significant protection (cr/cl: 121 ± 17 μ1/min). All treatments markedly diminished glomerular T cell and macrophage accumulation, reduced interferon-γ production by splenic T cells, prevented cutaneous DTH to the disease-initiating antigen and reduced antigen-specific immunoglobulin of the IgG2a and IgG3 isotypes. These data demonstrate that crescentic GN and renal impairment can be prevented by administration of Th2 cytokines and that this effect is associated with attenuation of the Th1 response to the disease-initiating antigen.     

The willingness to continue caring in family supporters of older people

Research has revealed the importance of characteristics of the supporter, the care-recipient, and circumstances of caregiving in the success or failure of community-based care of older people. The Dundee Study of Carers and Dementia examined factors associated with the maintenance and care of older people in the community, and with the impact of dementia on family supporters. Two hundred and twenty-eight family supporters of community-resident older people (≥65) (50% with dementia, 50% without, matched for age and sex) were interviewed. Supporters' responses to their relative's condition and circumstances, their ways of coping with stressful caregiving problems, and their willingness to continue their caregiving role, were assessed. Findings indicated that willingness to care and stress were associated in different ways with the supporter's response to his/her relative. Coping was found to be significantly associated with stress, response to relative, and willingness to care in only three out of a total of 45 tests. Willingness to care was positively associated with the coping behaviour internalization. The findings are discussed in the context of developing interventions for improving the well-being of supporters of an older relative in the community.     

Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01.

PURPOSE: To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix. PATIENTS AND METHODS: Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation. RESULTS: The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms. CONCLUSION: Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.     

Epidemiology of cerebral palsy in England and Scotland, 1984-9

AIMS—To report on the epidemiology of cerebral palsy in England and Scotland, to provide information on the prevalence of cerebral palsy and the severity of the disability or any co-morbidity.METHODS—Cerebral palsy registers were compiled from multiple sources of ascertainment covering all of Scotland and the counties of Merseyside, Cheshire, Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire in England. All cases of cerebral palsy born in 1984 to 1989, to mothers resident in the area, were included. Denominator number of live births and neonatal deaths for determining birthweight specific prevalence were obtained from birth and death registrations. Learning, manual, and ambulatory disabilities were graded for severity. Any co-existing sensory (hearing or visual) morbidity was also graded for severity.RESULTS—There were 789 411 live births in 1984-9, with 3651 neonatal deaths (neonatal mortality 4.6 per 1000 live births) and 1649cases of cerebral palsy—a cerebral palsy prevalence of 2.1 per 1000 neonatal survivors. The birthweight specific cerebral palsy prevalence ranged from 1.1 per 1000 neonatal survivors in infants weighing ?2500 g to 78.1 in infants weighing <1000 g. There was no significant time trend in prevalence of cerebral palsy in any of the birthweight groups, in contrast to the fall in neonatal mortality observed in all birthweight groups. Of the 1649 cases of cerebral palsy, 550 (33.4%) had severe ambulatory disability (no independent walking), 390 (23.7%) had severe manual disability (incapable of feeding or dressing unaided), 381 (23.1%) had severe learning disability (IQ <50), 146 (8.9%) had severe visual disability (vision <6/60 in the better eye) and 12 had severe hearing disability (>70 dB loss).CONCLUSIONS—Registers fill an important gap left by the lack of routine data on the prevalence of disability in children. The ability to record trends in the prevalence and the severity of the disability should inform those who have responsibility for providing services for children with disabilities.