Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study.

PURPOSE: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. MATERIALS AND METHODS: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm(3) or metastases in the brainstem. RESULTS: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. CONCLUSION: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary.

HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI.

To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.

Sequential versus concurrent chemo-radiotherapy in inoperable stage III non-small cell lung cancer.

AIM: To define the best sequence of radiotherapy and chemotherapy for inoperable stage III non-small cell lung (NSCL) tumours. MATERIALS AND METHODS: A systematic review was performed on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCL cancer stage III. The mean median survival time (MST) and mean overall survival (OS) percentages were derived for radiotherapy only, for sequential and for concurrent chemo-radiotherapy. RESULTS: The mean median survival duration +/- standard deviation for radiotherapy only was 10.4 +/- 1.8 months. For sequential chemo- and radiotherapy it was increased to 13.0 +/- 1.2 months. When radiotherapy in the sequential regimen was accompanied by chemotherapy, the mean median duration was 15.8 +/- 2.6 months. For concurrent radio-chemotherapy it was further increased to 16.4 +/- 2.7 months. The mean 2- and 3-year overall survivals for radiotherapy alone, sequential and concurrent radio-chemotherapy were 17.1 +/- 4.6 and 10, 23.8 +/- 6.3 and 18.5 +/- 7.0, and 32.5 +/- 8.7 and 25.7 +/- 6.3%, respectively. CONCLUSION: Concurrent chemo-radiotherapy demonstrated increased efficacy over sequential chemotherapy and radiotherapy and should be the treatment of choice. Further improvements may be obtained by optimising the conditions for concurrent chemo-radiotherapy.

Tumour control probability of stage III inoperable non-small cell lung tumours after sequential chemo-radiotherapy.

UNLABELLED: The aim of this study was to investigate the influence of the duration of waiting time between the end of induction chemotherapy and the start of radiotherapy on tumour control probability (TCP). PATIENTS AND METHODS: Twenty-three patients with inoperable stage III non-small cell lung cancer (NSCLC) received induction chemotherapy followed by radiotherapy. The mean waiting period between the end of induction chemotherapy and the start of radiotherapy was 80 days; in this period, the median tumour volume increased by a factor of about 6. The Poisson model for TCP and the linear-quadratic model were used to calculate changes in TCP in the waiting time. RESULTS: The 2-year survival of patients treated with curative intent was 8%, lower than the mean value of 26% derived from other studies. Assuming that radiotherapy started on the day of restaging or on the first day of radiotherapy (RT1), the calculated mean TCP at restaging was 13.3% and at RT1 was 0.5% for patients treated with curative intent. CONCLUSION: The calculated TCP decreased in the waiting period from 13.3 to less than 1%. Hence, the relatively long interval time between chemo- and radiotherapy had a deleterious effect on local control. We recommend the waiting time to be as short as possible.

Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy.

Induction chemotherapy of non-small-cell lung cancer (NSCLC) stage III with gemcitabine and cisplatin for downstaging of the tumour with the aim for further treatment with ionising radiation is one of the treatments for lung cancer patients. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, that is, the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth for patients with NSCLC. Interval times between the end of induction chemotherapy and date of diagnostic CT, planning CT and first day of radiotherapy were determined for 23 patients with NSCLC. Increase in gross tumour volume was measured for 18 patients by measuring the dimensions of the primary tumour and lymph node metastases on the diagnostic CT after induction chemotherapy and on the CT used for radiotherapy planning. For each patient, the volume doubling time was calculated from the time interval between the two CTs and ratio of the gross volumes on planning CT and diagnostic CT. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, and till first day of radiotherapy 80.3 (range 29-141) days. In all, 41% of potentially curable patients became incurable in the waiting period. The ratio of gross tumour volumes of the two CTs ranged from 1.1 to 81.8 and the tumour doubling times ranged from 8.3 to 171 days, with a mean value of 46 days and median value of 29 days. This is far less than the mean doubling time of NSCLC in untreated patients found in the literature. This study shows that in the time interval between the end of induction chemotherapy and the start of radiotherapy rapid tumour progression occurs as a result of accelerated tumour cell proliferation: mean tumour doubling times are much shorter than those in not treated tumours. As a consequence, the gain obtained with induction chemotherapy with regard to volume reduction was lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo- and radiotherapy to as short as possible.

Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits.

This is a retrospective analysis of 188 children who underwent total body irradiation (TBI) in one or two fractions before bone marrow transplantation (BMT) for a hematological disorder. While 139 children had eye shielding during TBI to decrease cataract formation, 49 did not. The blocks used for shielding caused cylindrical areas of decreased dose intensity in the brain. The aim of the study was to determine if there was an increased risk of relapse in the eyes or in the CNS after shielding of the eyes. The probability and severity of cataract formation with and without shielding were also evaluated. None of the 49 children without shielding had a relapse in their eyes or in the CNS after BMT. Of the children with shielding, none had a relapse in the eyes but two of the 139 (1.4%) had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21 evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts were present in eight of 21 (38%) patients without and two of 64 (3%) patients with shielding. The probability of staying cataract free for at least five years was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24 respectively. The relative risk of developing a cataract without shielding vs shielding was three (95% CI=1.5; 5.9). It appears that the incidence of relapse in the eyes and CNS is not increased when the eyes are shielded during TBI. Shielding increased the latency time of cataract formation and decreased the severity of cataracts.

Autologous and homologous transplantation of bovine spermatogonial stem cells.

The aim of this study was to develop a method for spermatogonial stem cell transplantation into the bovine testis. Five-month-old Holstein-Friesian calves were used and half of the calves were hemicastrated to allow autologous transplantation and the other half were used for homologous transplantation. Approximately 20 g of each testis was used for cell isolation. On average 106 cells per gram of testis containing about 70% type A spermatogonia were isolated. The cells were frozen in liquid nitrogen until transplantation. Testes were irradiated locally with 10-14 Gy of X-rays to deplete endogenous spermatogenesis. At 2 months after irradiation, cells (approximately 10 x 10(6) were injected into the rete testis through a long injection needle (18 gauge), using ultrasonography and an ultrasound contrast solution. At 2.5 months after transplantation, calves were castrated and samples of testes were taken for histological examination. After 2.5 months in the irradiated non-transplanted control testes, only 45% of the tubules contained type A spermatogonia. However, after autologous spermatogonial transplantation, >80% of the tubule cross-sections contained type A spermatogonia. In addition, only 20% of the tubules of the control testes contained spermatocytes and, except for a few tubules (5%) with round spermatids, no more advanced germ cells were found. After autologous spermatogonial transplantation, about 60% of the tubules contained spermatocytes; 30% contained spermatids and in about 15% of tubules spermatozoa were found. No improvement in spermatogonial repopulation was found after homologous transplantation. The results of this study demonstrate, for the first time, successful autologous transplantation of bovine spermatogonial stem cells resulting in a complete regeneration of spermatogenesis.

[Pregnancy and medical irradiation; summary and conclusions from the International Commission on Radiological Protection, Publication 84]. / Zwangerschap en straling; samenvatting en conclusies van Publicatie 84 van de International Commission on Radiological Protection.

Prenatal exposure to ionising radiation as used during most diagnostic procedures generally presents no increased risk of prenatal death, malformation or impairment of mental development (i.e. deterministic effects) compared to the background incidence of these entities. Higher doses of radiation used in therapeutic procedures can result in significant foetal harm. In general, malformations only occur above a threshold dose of 100-200 mGy. These doses are not normally reached with most properly executed diagnostic procedures. During the period from 8 to 25 weeks after conception, the central nervous system is particularly sensitive to radiation. Foetal doses in excess of about 100 mGy may result in a decrease in IQ. Between 8-15 weeks after conception, a foetal dose of 1000 mGy (1 Gy) reduces IQ by about 30 points. This reduction is less marked during the period from 16-25 weeks. At foetal doses of 1000 mGy in the period from 8 to 15 weeks after conception the risk of severe mental retardation is about 40%. During the period from 16 to 25 weeks, this risk is practically zero at a dose of 1000 mGy. Radiation exposure of the embryo/foetus is associated with an increased risk of tumour induction (stochastic effect). Recent absolute risk estimates for fatal cancer risk for ages 0-15 year after in utero irradiation have been estimated to be 6% per Gy (0.06% per 10 mGy). For the whole life span this risk is about 15% per Gy (0.15% per 10 mGy). Pre-conception irradiation of either parent's gonads has not been shown to result in increased cancer or malformations in the children.

Role for c-Abl and p73 in the radiation response of male germ cells.

p53 plays a central role in the induction of apoptosis of spermatogonia in response to ionizing radiation. In p53(-/-) testes, however, spermatogonial apoptosis still can be induced by ionizing radiation, so p53 independent apoptotic pathways must exist in spermatogonia. Here we show that the p53 homologues p63 and p73 are present in the testis and that p73, but not p63, is localized in the cytoplasm of spermatogonia. Unlike p53, neither p63 nor p73 protein levels were found to increase after a dose of 4 Gy of X-rays. Although p73 protein levels did not increase, its interaction with the non-receptor tyrosine kinase c-Abl and its phosphorylation on tyrosine residues did. c-Abl and p73 co-localize in the cytoplasm of spermatogonia and spermatocytes and in the residual bodies. Furthermore, c-Abl protein levels increase after irradiation. p63 was not found to co-localize or interact with c-Abl neither before nor after irradiation. In conclusion, in the testis ionizing radiation elevates cytoplasmic c-Abl that in turn interacts with p73. This may represent an additional, cytoplasmic, apoptotic pathway. Although less efficient than the p53 route, this pathway may cause spermatogonial apoptosis as observed in p53 deficient mice.

A moderate elevation of blood glucose level increases the effectiveness of thermoradiotherapy in a rat tumor model. I. Relative contributions of glucose and heating to tumor acidification.

PURPOSE: To establish dose-effect relationships for tumor acidification induced by heat and glucose as a basis for testing the value of adding glucose administration to combined heat and x-ray treatment at clinically achievable glucose and temperature levels. METHODS AND MATERIALS: Rhabdomyosarcoma BA1112 was grown s.c. in the upper leg of 16-20-week-old Wag/Rij rats. Animals were given 2 consecutive 100-min periods of saline (S) or glucose (G) infusion, while keeping tumor temperature at 37 degrees, 42 degrees, or 43 degrees C for 1 or 2 periods, in various combinations, each involving 6 animals. Glucose was infused i.v. as a 20% solution at 2.4-3 g/kg/h. Tumors were heated using 2,450-MHz electromagnetic radiation, and tumor pH was measured using a 0.7 mm fiberoptic probe. RESULTS: Mean overall baseline pH was 7.00 (SD 0.10). The change induced by G37G43 (i.e., glucose infusion for a full 200 min, first 100 min at 37 degrees C, final 100 min at 43 degrees C) was -0.48 +/- 0.03 (SEM) pH units, and -0.17 +/- 0.03 for S37S43. The effect of G37G42 was -0.37 +/- 0.03 pH units, compared with -0.08 +/- 0.02 for S37S42 and -0.28 +/- 0.04 for glucose alone (G37G37). Glucose was less effective when given after or fully parallel to heating: -0.21 +/- 0.02 pH units for S43G37 and -0.37 +/- 0.02 for G43G43. CONCLUSION: The glucose-induced tumor pH drop is much more pronounced than that induced by heat, both of which are dose dependent. The effects of glucose and heat seem additive if heating is started when glucose-induced acidification has reached its plateau level, but the overall effect is diminished if administration is fully simultaneous or in reversed order. Schedule G37G43 is optimal with respect to tumor acidification. Its predicted superiority in thermoradiotherapy as compared with S37S42, S37S43, and G37G42 treatment regimens was confirmed in a subsequent experimental tumor control study.

A moderate elevation of blood glucose level increases the effectiveness of thermoradiotherapy in a rat tumor model II. Improved tumor control at clinically achievable temperatures.

PURPOSE: To assess the therapeutic gain (at the TCD(50) level) that can be obtained by boosting thermoradiotherapy with intravenous glucose infusion at different temperatures. This completes our series of studies to determine the optimal conditions and the effectiveness of glucose administration at clinically achievable glucose levels and treatment temperatures. METHODS AND MATERIALS: Subcutaneous rat rhabdomyosarcoma BA1112 was irradiated with graded single doses of 300-kV X-rays (dose range 0-60 Gy). Fifteen minutes after irradiation, a 100-min intravenous infusion was started, consisting of either glucose (20% solution, 2.4-3 g/kg/h) or saline as a control. Then heat was applied to the tumors at 42 degrees C or 43 degrees C (water bath) during a subsequent 100-min period of infusion. Tumor control was scored as the absence of palpable growth at 100 days after treatment. RESULTS: Glucose infusion enhanced tumor control independent of temperature in the range 42-43 degrees C. At 42 degrees C, the TCD(50) for X-irradiation decreased by 5.9 Gy (SEM 1.8 Gy), from 41.6 (1.6) to 35.7 (1.5) Gy, and at 43 degrees C from 33.3 (1.6) to 27.3 (1.5) Gy, representing a glucose enhancement ratio of approximately 1.2. At doses corresponding to the TCD(50) at either 42 or 43 degrees C, the addition of glucose increased tumor control from 50% to 70%. An enhancement ratio of 2.1 was found for the combination of irradiation, glucose infusion, and heating at 43 degrees C, with respect to irradiation alone (TCD(50) 56.3 Gy, reanalyzed earlier data). The contribution of combined heat and glucose to tumor control represented an additive effect, probably on the hypoxic cell population. CONCLUSION: Moderate glucose administration (blood concentration 300 mg/100 mL) sizably improves experimental tumor control after combined X-irradiation and hyperthermia under clinically feasible conditions. Clinical treatment should benefit from this additional modality, in particular if unsatisfactory local control rates are due to insufficient heating. The therapeutic gain has to be evaluated further in clinical studies.

Proliferative capacity in head and neck cancer.

BACKGROUND: Shortening of overall treatment time (accelerated radiotherapy) appears to result in an increase of the efficacy of irradiation. In this study, we compared the proliferative capacity between tumors originating in different sites of the head and neck region. Tumors with a large proliferating capacity might, theoretically, benefit most from accelerated radiotherapy. MATERIAL AND METHODS: BrdUrd was administered intravenously in patients with head and neck carcinomas. Tumor samples were analyzed with flow cytometry. T and N stages were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: No significant differences in proliferation parameters were observed with respect to site of origin of head and neck tumors. For T3/T4 tumors, DNA ploidy is an important tumor characteristic: G1- and S-phase fractions, labeling index, and tumor doubling time Tpot differences were statistically significant; the aneuploid tumors showed the largest proliferative potential. CONCLUSIONS: (1) In general, no significant differences in proliferation parameters were observed with respect to site of origin. (2) Aneuploid head and neck tumors have a higher proliferative capacity than diploid ones, they might benefit most from accelerated irradiation.

Involvement of the D-type cyclins in germ cell proliferation and differentiation in the mouse.

Using immunohistochemistry, the expression of the D-type cyclin proteins was studied in the developing and adult mouse testis. Both during testicular development and in adult testis, cyclin D(1) is expressed only in proliferating gonocytes and spermatogonia, indicating a role for cyclin D(1) in spermatogonial proliferation, in particular during the G(1)/S phase transition. Cyclin D(2) is first expressed at the start of spermatogenesis when gonocytes produce A(1) spermatogonia. In the adult testis, cyclin D(2) is expressed in spermatogonia around stage VIII of the seminiferous epithelium when A(al) spermatogonia differentiate into A(1) spermatogonia and also in spermatocytes and spermatids. To further elucidate the role of cyclin D(2) during spermatogenesis, cyclin D(2) expression was studied in vitamin A-deficient testis. Cyclin D(2) was not expressed in the undifferentiated A spermatogonia in vitamin A-deficient testis but was strongly induced in these cells after the induction of differentiation of most of these cells into A(1) spermatogonia by administration of retinoic acid. Overall, cyclin D(2) seems to play a role at the crucial differentiation step of undifferentiated spermatogonia into A(1) spermatogonia. Cyclin D(3) is expressed in both proliferating and quiescent gonocytes during testis development. Cyclin D(3) expression was found in terminally differentiated Sertoli cells, in Leydig cells, and in spermatogonia in adult testis. Hence, although cyclin D(3) may control G(1)/S transition in spermatogonia, it probably has a different role in Sertoli and Leydig cells. In conclusion, the three D-type cyclins are differentially expressed during spermatogenesis. In spermatogonia, cyclins D(1) and D(3) seem to be involved in cell cycle regulation, whereas cyclin D(2) likely has a role in spermatogonial differentiation.

Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters.

PURPOSE: To determine prospectively the cataract-free interval (latency time) after total body irradiation (TBI) and bone marrow transplantation (BMT) and to assess accurately the final severity of the cataract. METHODS AND MATERIALS: Ninety-three of the patients who received TBI as a part of their conditioning regimen for BMT between 1982 and 1995 were followed with respect to cataract formation. Included were only patients who had a follow-up period of at least 23 months. TBI was applied in one fraction of 8 Gy or two fractions of 5 or 6 Gy. Cataract-free period was assessed and in 56 patients, who could be followed until stabilization of the cataract had occurred, final severity of the cataract was determined using a classification system. With respect to final severity, two groups were analyzed: subclinical low-grade cataract and high-grade cataract. Cataract-free period and final severity were determined with respect to type of transplantation, TBI dose, and posttransplant variables such as graft versus host disease (GVHD) and steroid treatment. RESULTS: Cataract incidence of the analyzed patients was 89%. Median time to develop a cataract was 58 months for autologous transplanted patients. For allogeneic transplanted patients treated or not treated with steroids, median times were 33 and 46 months, respectively. Final severity was not significantly different for autologous or allogeneic patients. In allogeneic patients, however, final severity was significantly different for patients who had or had not been treated with steroids for GVHD: 93% versus 35% high-grade cataract, respectively. Final severity was also different for patients receiving 1 x 8 or 2 x 5 Gy TBI, from patients receiving 2 x 6 Gy as conditioning therapy: 33% versus 79% high-grade cataract, respectively. The group of patients receiving 2 x 6 Gy comprised, however, more patients with steroid treatment for GVHD. So the high percentage of high-grade cataract in the 2 x 6 Gy group might also have been caused to a significant extent by steroid treatment. The percentage of patients with high-grade cataract was lower in allogeneic transplanted patients without steroid treatment for GVHD than in autologous transplanted patients: 35% versus 48%. An explanation for this could be pretransplant therapy containing high-dose steroids. CONCLUSIONS: After high-dose-rate TBI in one or two fractions, steroids for GVHD influence latency time of a cataract and are of great importance for the severity the cataract finally attains. Although a cataract will develop in all patients, a clinically important high-grade cataract is relatively infrequent in patients not treated with steroids. Pretransplant therapy might also influence final severity of cataract.

Influence of p53 and bcl-2 on proliferative activity and treatment outcome in head and neck cancer patients.

Knowledge about the influence of biomarkers on cell proliferative activity might explain differences in radiosensitivity between head and neck tumors and might improve patient selection for the most optimal treatment strategy. p53 and bcl-2 protein expression were determined immunohistochemically in 56 head and neck cancer patients, treated by surgery only in five cases and by radiotherapy, with or without surgery, in 51 cases. Relationships with various cell proliferation markers, determined by flow-cytometry (G1-phase fraction, S-phase fraction, BrdUrd-labeling index, duration of S-phase and potential doubling time) were investigated. Associations between these cell proliferation parameters, on the one hand, and both p53 and bcl-2, on the other, were not found. Furthermore, p53 and bcl-2 expression were both not related to clinicopathological parameters (T- and N-stage, site, grade) and did not affect loco-regional recurrence-free survival and/or disease-free survival. We could not find a prognostic value for both p53 and bcl-2 protein expression to differentiate radiosensitive from radioresistant head and neck tumors.

Apoptosis regulation in the testis: involvement of Bcl-2 family members.

Using immunohistochemical techniques and Western blot analysis, the possible role of Bcl-2 family members Bax, Bcl-2, Bcl-x(s), and Bcl-x(l) in male germ cell density-related apoptosis and DNA damage induced apoptosis was studied. The apoptosis inducer Bax was localized in all mouse and human testicular cell types, but despite the fact that irradiation induces its transcriptional activator, p53 in the human, Bax expression did not change after irradiation. The apoptosis inhibitor Bcl-2 appeared to be present in late spermatocytes and spermatids and was up-regulated in these cells after a dose of 4 Gy of X-rays. Finally, Bcl-x was expressed in both the mouse and human testis. The apoptosis inhibiting long transcripts of Bcl-x, Bcl-x(l), were expressed in spermatogonia and spermatocytes and were up-regulated after X-irradiation. The apoptosis inducing shorter form of Bcl-x, Bcl-x(s), was found to be expressed only in somatic cells, like peritubular and Leydig cells. While Bax is important in germ cell density regulation, Bax expression did not change after DNA damage inflicted by X-radiation. Hence, spermatogonial apoptosis after X-irradiation may not be induced via the apoptosis inducer Bax. Furthermore, as Bcl-x(l), but not Bcl-2, is present in spermatogonia and spermatocytes, Bcl-x(l) may regulate germ cell density, possibly in cooperation with Bax. As Bcl-x(l) expression is enhanced after irradiation, this protein may also have a role in the response of spermatogonia and spermatocytes to irradiation.

Single-dose radiotherapy for painful bone metastases.

BACKGROUND: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. METHODS: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare therapy schemes which each other for the iso-effect pain relief. RESULTS: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. CONCLUSION: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief.

[Health Council Report 'Radiofrequency electromagnetic fields (300 Hz-300 GHz). The Health Council of the Netherlands]. / Gezondheidsraad-rapport 'Radiofrequente elektromagnetische velden (300 Hz-300 GHz)'.

The Health Council of the Netherlands in 1997 issued a report updating the guidelines for maximum acceptable exposure to radiofrequency electromagnetic fields formulated in 1975. The new recommendations are based on thermal effects for frequencies over 10 MHz. The committee considers the results of studies indicating non-thermal effects such as direct damage to DNA, not reliable enough to be used in setting exposure limits. Electromagnetic interference by electromagnetic fields generated by hand-held telephones may indirectly result in threats to health if vital medical equipment is affected. The committee advises people wearing an implanted pacemaker not to carry a portable telephone that is in stand-by mode in close proximity to the pacemaker; a minimum distance of 15 cm should be observed.