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Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group.

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.

Aged↗

High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: long-term results of a radiation dose escalation study.

PURPOSE: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes > or =1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. RESULTS: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. CONCLUSIONS: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy.

Adult↗

The radiation accident in Georgia: clinical appearance and diagnosis of cutaneous radiation syndrome.

BACKGROUND: Eleven male Georgian soldiers were accidentally exposed to radiation by cesium 137 during their training in a military exercise camp in Lilo, Georgia between November 1996 and May 1997. OBJECTIVE: The characteristic sequelae of accidental cutaneous irradiation and available diagnostic methods are described. METHODS: Magnetic resonance imaging (MRI) of radiation ulcers was performed in all patients; thermography was performed in 2. In 7 patients ulcers and white macules were examined with high-frequency 20 MHz sonography; histologic results were obtained from all patients. RESULTS: Predominant lesions were radiation ulcers in 11 patients and white hairless macules in 7. MRI showed ulcers down to the muscles and an increase of signal intensity in the musculature in 9 cases. The corresponding muscle histology demonstrated vasculitis in 7 patients and necrosis in 2. In 2 patients, MRI signal intensity of the musculature was normal. In 3 patients, 20 MHz sonography showed dermal defects; 1 patient had cutaneous fibrosis. Thermography demonstrated hypothermic zones with extended inflammatory zones adjacent to the radiation ulcers in both patients examined. CONCLUSION: High-frequency 20 MHz sonography, MRI, and thermography are useful noninvasive methods for diagnosis of the extent of cutaneous radiation syndrome and for therapy planning.

Adult↗

Absence of thoracic radiation myelitis after hyperfractionated radiation therapy with and without concurrent chemotherapy for Stage III nonsmall-cell lung cancer.

PURPOSE: To investigate whether thoracic spinal cord dose of 50.4 Gy given via 1.2 Gy b.i.d. fractionation carries a risk of developing radiation myelitis during studies using hyperfractionated radiation therapy (HFX RT) with and without concurrent chemotherapy (CHT). METHODS AND MATERIALS: Of 300 patients with Stage III nonsmall-cell lung cancer (NSCLC) who were treated on two consecutive Phase III studies, 158 patients received 50.4 Gy to a portion of their spinal cord and survived > 1 year after the beginning of the therapy. RESULTS: None of these 158 patients developed thoracic radiation myelitis. Therefore, influence of potentially contributing factors on the occurrence of radiation myelitis, such as interfraction interval, or those unproven yet, such as cord length or administration of concurrent CHT, was not possible to investigate. CONCLUSION: Given the continuing interest in HFX RT and encouraging results obtained in studies in lung cancer, further investigation is needed to get more informations about risks of developing thoracic radiation myelitis with this cord dose.

Adult↗

Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms.

PURPOSE: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation with graded doses of X-rays. METHODS: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 mg/kg) was administered intraperitoneally, 1 hour prior to irradiation. Saliva samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irradiation. The parotid salivary flow rate (microl/min) was used as a parameter for the assessment of parotid gland function. RESULTS: Our data confirm that a single prophylactic treatment of pilocarpine can attenuate radiation-induced loss of gland function. Surprisingly, the effect of pilocarpine was not restricted to the irradiated gland only. Pilocarpine also enhanced the flow rate in the contralateral, nonirradiated gland. The latter effect was found for all doses above 10 Gy and became apparent around 7 days after the radiation treatment. The effectiveness of pilocarpine to attenuate function loss in the irradiated gland decreased with increasing dose and was lost after single doses of 30 Gy. CONCLUSIONS: Our data provide direct evidence that increasing the compensatory potential of the nondamaged gland, at least in part, underlies the "radioprotective effect" of pilocarpine in case of unilateral radiation. The ability of pilocarpine to ameliorate the early radiation-induced impairment of the parotid gland function in the irradiated gland may therefore be dependent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal.

Animals↗

Ionizing radiation and mitogenetic radiation: two links of the same energetic chain in a biological cell.

Present research demonstrates that the excitation of living systems by high energy/low doses of ionizing radiation (IR) initiates prolonged secondary ultraviolet (UV) range emission that influences biota. When doses of this energy are too high, the process of energy or radiation absorption by the cells causes negative changes (i.e. negative mutations or death). When these doses are sufficiently low, vital processes inside the cells are stimulated and can create positive changes. This paper proposes a common denomination for mechanisms of UV and ionizing radiation when interacting with living cells, underlying both its mitogenetic effect and radiation hormesis. Data from radon exposure in chronically exposed nuclear workers, acutely exposed Hiroshima and Nagasaki victims and observers of atmospheric nuclear explosions, combined with animal results, present irrefutable evidence that low doses of IR are beneficial. As a conclusion the author postulates the possibility of new methods of therapy regarding the use of IR and mitogenetic radiation. This paper has been written to encourage debate regarding possible future benefits that may be derived from low level doses of IR exposure in the general population.

Animals↗

[Malignant brain tumors after radiation - glioblastomas after operation and radiation of meningiomas - 2 case reports].

The authors report 2 cases of glioblastomas subsequent to radiation of intracranial tumors. In the first case, a 47-year old man received radiation therapy after subtotal removal of a temporobasal meningioma. In the second case, a 52-year old women underwent operation of an atypical falcine meningioma and was irradiated postoperatively. - After radiation of meningiomas the development of glioblastomas is described as a rare complication in the literature. A literature analysis of 49 radiation induced tumors revealed that there was no correlation between the radiation dosage and time interval of appearance of the second tumor.

Female↗

Heterogeneous radiation and heat sensitivity in vitro of human melanoma xenograft lines established from different lesions in the same patient. Comparisons with the radiation and heat sensitivity of cells isolated from the donor patient's surgical specimens.

Human melanoma xenograft lines were established in athymic nude mice (BALB/c-nu/nu/BOM) from the primary tumour (OKL-PRI), a s.c. metastasis (OKL-SCM) and a lymph node metastasis (OKL-LNM) in the same patient. The three lines differed in growth rate, melanin content, and radiation and heat sensitivity in vitro. The OKL-PRI line grew more slowly than the OKL-SCM and OKL-LNM lines and was the only line that synthesized significant amounts of melanin. The D0 values were 0.96 +/- 0.07 Gy, 0.87 +/- 0.07 Gy and 1.52 +/- 0.09 Gy (X-rays); 143 +/- 21 min, 109 +/- 12 min and 195 +/- 40 min (heat, 42.5 degrees C); and 21.3 +/- 2.7 min, 15.3 +/- 1.7 min and 26.7 +/- 3.0 min (heat, 44.5 degrees C) for the OKL-PRI, OKL-SCM and OKL-LNM line, respectively. The ranking of the lines in treatment sensitivity was equal for radiation and heat. The radiation and heat sensitivities were similar to those for cells isolated directly from the surgical specimens of the donor patient. The lines were thus established from a single neoplastic disease without artificial cloning in vitro or in vivo, and the cellular radiation and heat sensitivity did not change during the establishment procedure, suggesting that they constitute a relevant experimental model system for studies of clonal tumour heterogeneity in response to radiation and hyperthermia treatments.

Acclimatization↗

Radiation safety instruction for non-radiation workers.

In today's society, neglecting to provide adequate hazard-awareness instruction to workers can be successfully used to file suit against institutions where radioactive material (RAM) or radiation generating devices (RGDs) are used. Because of the lack of instruction, in some cases, just the perceived risk (even where no significant exposure to radiation existed) has proven to be more important than the actual risk. Groups of non-radiation workers such as custodian, maintenance and laboratory personnel, whose duties may require them to work in the vicinity of RAM and RGDs, sometimes do not receive proper hazard-awareness instruction. Misinterpretation of the applicable hazard-awareness regulations is a reason why institutions sometimes fail to instruct their workers. The objectives of this paper are to help radiation safety program managers become more aware of the importance of having well-instructed non-radiological personnel and to develop and provide basic information to help implement an effective hazard-awareness instruction program for workers. Topics discussed in this paper include regulatory aspects regarding the instruction to non-radiation workers, a list of radiological incidents that could have been prevented with proper instruction to workers and recommendations for the development and implementation of an effective instruction program.

Curriculum↗

Evaluation of external radiation exposure rate from radioiodine-treated hyperthyroid patients and radiation safety considerations.

Hyperthyroid patients treated with radioiodine (131I) pose an external radiation risk to individuals who come into close contact with them. In order to determine changes in levels of external radiation with time in relation to the dose administered, 38 hyperthyroid patients being treated with 131I were evaluated Thyroid uptake, plasma T3, T4 and TSH levels were measured prior to treatment. Using a Geiger-Muller probe, levels of external radiation were measured at distances of 0.3, 0.6, 1.0 and 2.0 m from the patient -at the level at which the maximum activity was recorded -30 min, 1, 3, 7 and 10 days post-therapy. The patients were split into two groups. Group I comprised 22 patients treated with < or = 370 MBq 131I, 5 (23%) of whom registered > 0.46 mC kg-1 at a distance of 1.0 m 30 min post-therapy. Group II comprised 16 patients treated with > 370 MBq 131I, 13 (81%) of whom registered 0.46 mC kg-1 at a distance of 1.0 m one day post-therapy. At 3 days in Group I and 7 days in Group II, the estimated total radiation exposure rates were found to exceed the 1994 US Nuclear Regulatory Commission dose limits for children and pregnant women. Based on the results obtained, we present some guidelines intended to prevent the public from unnecessary radiation exposures.

Adult↗

The use of radiation surveys to estimate the radiation effective dose to visitors of hospitalized patients--a theoretical study.

Members of the public visiting hospitalized patients undergoing nuclear medicine procedures or brachytherapy are exposed to radiation emanating from the patient. The radiation protection staff at the hospital is responsible for ensuring that the doses to these visitors are kept as low as is reasonably achievable and are maintained below applicable regulatory limits. These limits are normally expressed in terms of the effective dose to the visitor. Direct measurement of the effective dose, however, is not feasible, and the use of a quantity that provides a reasonable estimate, referred to as a surrogate, is required. This study used Monte Carlo radiation transport calculations to examine the feasibility of using bedside survey results, in units of roentgens per hour, as a surrogate for estimating the effective dose to a person who may be present at the survey location. The Monte Carlo code used in this work was MCNP Version 5. In these calculations, both the patient and the visitor were modeled using modified Medical Internal Radiation Dose anthropomorphic phantoms. Radioactive material that emitted monoenergetic photons was located in several of the patient's organs in turn, and the bedside exposure rates and the effective doses at the same location were calculated. The calculations were repeated for several visitor locations, both at bedside along the length of the bed, and at increasing distances from the bed. The ratios of the exposure rates to the effective dose rates at each location gave an indication of the utility of the exposure rate measurements in providing a reasonable estimate of the effective dose. The results indicated that the survey data provided estimates of the effective dose within recommended accuracy for many exposure situations, but underestimated the effective dose to the visitor for other situations, especially locations close to bedside and for lower energy radiations. Use of appropriate correction factors based on this work could improve the utility of the survey data for the underestimated situations, and the exposure rate data could still be used to estimate the dose to a visitor within recommended accuracy, provided the estimated dose does not approach too closely to the applicable limit.

Data Collection↗

Annual exposures to carcinogenic radiation from the sun at different latitudes and amplification factors related to ozone depletion. The use of different geometrical representations of the skin surface receiving the ultraviolet radiation.

In most calculations of annual fluences of carcinogenic light as well as of the radiation amplification factor and of biological amplification factors associated with ozone depletions, the radiation is assumed to fall on a horizontally oriented plane surface. This is obviously a bad approximation of the surface of the human body. In order to evaluate the importance of using a realistic geometric representation of the surface of the human body we here present calculations of the flux of carcinogenically effective radiation falling on three different bodies: a vertically standing cylinder, a sphere and a horizontally oriented surface. The exposure to carcinogenic radiation depends strongly on the surface geometry. However we find that the radiation amplification factors are almost independent of the surface geometry chosen. The biological amplification factors for the three geometrical representations are also similar to within 20%. The total amplification factor for the increase in the incidence of non-melanoma skin cancer related to ozone depletion is about 17% larger when a cylindrical representation is used compared to when a plane horizontal surface is considered.

Humans↗

Effect of physiological age on radiation resistance of some bacteria that are highly radiation resistant.

Physiological age-dependent variation in radiation resistance was studied for three bacteria that are highly radiation resistant: Micrococcus radiodurans, Micrococcus sp. isolate C-3, and Moraxella sp. isolate 4. Stationary-phase cultures of M. radiodurans and isolate C-3 were much more resistant to gamma radiation than were log-phase cultures. This pattern of relative resistance was reversed for isolate 4. Resistance of isolate 4 to UV light was also greater during log phase, although heat resistance and NaCl tolerance after heat stress were greater during stationary phase. Radiation-induced injury of isolate 4 compared with injury of Escherichia coli B suggested that the injury process, as well as the lethal process, was affected by growth phase. The hypothesis that growth rate affects radiation resistance was tested, and results were interpreted in light of the probable confounding effect of methods used to alter growth rates of bacteria. These results indicate that dose-response experiments should be designed to measure survival during the most resistant growth phase of the organism under study. This timing is particularly important when extrapolations of survival results might be made to potential irradiation processes for foods.

Acinetobacter↗

Intracoronary radiation therapy improves the clinical and angiographic outcomes of diffuse in-stent restenotic lesions: results of the Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST) Studies.

BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial for long lesions (Long WRIST) was designed to determine the safety and efficacy of vascular brachytherapy for the treatment of diffuse in-stent restenosis. METHODS AND RESULTS: A total of 120 patients with diffuse in-stent restenosis in native coronary arteries (lesion length, 36 to 80 mm) were randomized for either radiation with 192Ir with 15 Gy at 2 mm from the source axis or placebo. After enrollment, 120 additional patients with the same inclusion criteria were treated with 192Ir with 18 Gy and included in the Long WRIST High Dose registry. Antiplatelet therapy was initially prescribed for 1 month and was extended to 6 months in the last 60 patients of the Long WRIST High Dose registry. At 6 months, the binary angiographic restenosis rate was 73%, 45%, and 38% in the placebo, 15 Gy, and 18 Gy radiated groups, respectively (P<0.05). At 1 year, the primary clinical end point of major cardiac events was 63% in the placebo group and 42% in the radiated group with 15 Gy (P<0.05). The major cardiac event rate was further reduced with 18 Gy (22%; P<0.05 versus 15 Gy). Late thrombosis was 12%, 15%, and 9% in the placebo group, 15 Gy group with 1 month of antiplatelet therapy, and 18 Gy group with 6 months of antiplatelet therapy, respectively. CONCLUSIONS: Vascular brachytherapy with 192Ir is safe and reduces the rate of recurrent restenosis in diffuse in-stent restenosis. The efficacy of vascular brachytherapy on angiographic and clinical outcomes is enhanced with a radiation dose of 18 Gy and prolonged antiplatelet therapy.

Brachytherapy↗

Radiation therapy in the treatment of meningioma: the Joint Center for Radiation Therapy experience 1970 to 1982.

The standard treatment for meningioma is complete resection. However, complete resection is often not possible because of tumor location and extent. To evaluate the usefulness of radiation therapy in patients with unresected or residual tumor, we reviewed the Joint Center for Radiation Therapy experience from 1970 to 1982 (n = 31). Histologic diagnosis was available in 27 patients. The patients were treated with megavoltage radiation to a mean dose of 5,280 rad (3,780 to 6,050 rad) in 180- to 200-rad daily fractions using multiple static or rotational fields. The median follow-up period was 45 months, with a range of four to 156 months. The overall four-year relapse-free survival (RFS) rate was 72%. All relapses occurred within the first 37 months; the mean time to relapse was 31 months. The four-year RFS was the same whether patients were treated at initial presentation or after recurrence (74% v 67%, respectively). There was no difference in RFS for patients treated after partial resection or those patients with no resection (76% v 64%). No patients with malignant meningioma were relapse free three years after radiation therapy. Complications included decreased auditory acuity in three patients and retinopathy in one patient. These data suggest that moderate dose radiation therapy can offer long-term symptom-free survival with few complications in patients having unresected or partially resected benign meningioma.

Combined Modality Therapy↗

External radiation protection audit in National Health Service hospitals. Radiation protecgtion advisors (RPA) of the Nottingham City Hospital NHS Trust and the Oxford Radcliffe Hospital NHS Trust.

Radiation protection advisers are accustomed to carrying out internal audit in organizations for which they provide services but, traditionally, external audit has not been a part of the radiation protection adviser function. To provide an external audit function, two teams of radiation protection advisers undertook external radiation protection audits of their respective organizations, including the radiation protection adviser function itself. These audits were more representative of audits or inspections carried out by government agencies, for example the Health and Safety Executive and the former Inspectorate of Pollution, now the Environment Agency. Subsequently, reports, including recommendations for remedial action, were prepared for each management by the external auditors. The process of setting up and carrying out the external audits is described. Guidelines are suggested for those seeking to carry out an external audit.

England↗

Radiation research society 1952-2002. Physics as an element of radiation research.

Since its inception in 1954, Radiation Research has published an estimated total of about 8700 scientific articles up to August 2001, about 520, or roughly 6%, of which are primarily related to physics. This average of about 11 articles per year indicates steadily continuing contributions by physicists, though there are appreciable fluctuations from year to year. These works of physicists concern radiation sources, dosimetry, instrumentation for measurements of radiation effects, fundamentals of radiation physics, mechanisms of radiation actions, and applications. In this review, we have selected some notable accomplishments for discussion and present an outlook for the future.

History, 20th Century↗

Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results.

One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy.

Adenocarcinoma↗