Biomedical subjects

J Bernier

Publications and source records attributed to J Bernier.

At least 19 recordsLinked to original sources

PubMed2001

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Adult↗

PubMed2000

Improved immune functions with administration of a low-fat diet in a burn animal model.

The purpose of this study was to characterize the impact of a low-fat (LF; 1% fat) diet, a high-fat (HF; 25% fat) diet, and a standard (SD; 5% fat) diet on immune and oxidative parameters in a 20% body surface area burn animal model fed ad libitum for 10 days postinjury. Although the mechanisms are poorly understood, the amount of dietary lipid in nutritional support has been shown to have immunomodulatory effects after burn injury. Burned mice fed the LF diet showed a normal response in activated splenocyte proliferation compared to burned animals that received the SD or HF diet. Animals fed the SD and HF diets presented increased production of nitric oxide and prostaglandin E2 response after burn injury, which is associated with inhibited splenocyte proliferation. The total thiol concentration in spleen cells from burned animals kept on the HF diet was significantly higher than that in unburned animals, while no increase in these oxidative parameters was observed in LF-fed burned animals. Moreover, the LF diet significantly reduced hepatic lipid peroxidation, as measured by malonaldehyde concentration, compared to the other two diets. These results suggest that the administration of a LF diet in mice after a burn injury prevents inhibition of in vitro splenocyte proliferation and reduces the intensity of oxidative stress.

Animal Feed↗

PubMed2000

A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells.

DNA non-homologous end joining, the major mechanism for the repair of DNA double-strands breaks (DSB) in mammalian cells requires the DNA-dependent protein kinase (DNA-PK), a complex composed of a large catalytic subunit of 460 kDa (DNA-PKcs) and the heterodimer Ku70-Ku80 that binds to double-stranded DNA ends. Mutations in any of the three subunits of DNA-PK lead to extreme radiosensitivity and DSB repair deficiency. Here we show that the 283 C-terminal amino acids of Ku80 introduced into the Chinese hamster ovary cell line CHO-K1 have a dominant negative effect. Expression of Ku(449-732) in CHO cells was verified by northern blot analysis and resulted in decreased Ku-dependent DNA end-binding activity, a diminished capacity to repair DSBs as determined by pulsed field gel electrophoresis and decreased radioresistance determined by clonogenic survival. The stable modifications observed at the molecular and cellular level suggest that this fragment of Ku80 confers a dominant negative effect providing an important mechanism to sensitise radioresistant cells.

Animals↗

PubMed2000

Classical (HIV-negative) cutaneous Kaposi's sarcoma: a case report and a short review of the literature.

Classical Kaposi's sarcoma is a sporadic disease with a markedly higher incidence in the Mediterranean area. The two original forms of this disease, the Caucasian (classical) and the African, are now well-documented entities. The immunosuppression-related form is a new, recently described subset of the disease, arising from the human immune deficiency virus (HIV) infection and/or the widespread use of immunosuppressive treatments. Cutaneous lesions are the most common manifestation of classical Kaposi's sarcoma. The case described in the present report is characterised by a history of slowly evolving disease affecting the lower extremities without spread to thoracic or abdominal organs, a lengthy remission following initial radiation therapy, and local relapse with a further remission after a second course of radiation. Current treatments, in particular radiation therapy, achieve disease control or at least control of disease-related symptoms (mainly pain) in most cases, even when cure is not possible.

Aged↗

PubMed2000

Increased burn-induced immunosuppression in lipopolysaccharide-resistant mice.

Severe burns induce a state of immunosuppression, and the inflammatory response after burn injury may play a role in this phenomenon. This study examined the effect of the inflammatory response to endotoxin on burn-induced immunosuppression and oxidative stress. An endotoxin-resistant mouse strain (C3H/HeJ) and a normally responding mouse strain (C3H/HeN) were compared. The mice were separated into three groups of five animals for each experimental day: (1) saline, (2) buprenorphine, and (3) buprenorphine and 20% total body surface area burn. All animals were fed ad libitum. The inflammatory response was studied at 1, 4, 7, 10, and 14 days postburn. Proliferation of activated splenocytes in burn mice was significantly lower on days 7, 10, and 14 for the C3H/HeJ strain and on days 4 and 10 for the C3H/HeN strain. Globally, C3H/HeJ presented stronger immune suppression than C3H/HeN. Oxidative stress parameters (liver malonaldehyde, spleen metabolic activity, and thiol concentrations) were higher in endotoxin-resistant mice than in the control strain. Impairment of the inflammatory response was more pronounced and oxidative stress was greater in endotoxin-resistant burn mice than in normal burn controls. Buprenorphine administration was not related to depression of these immune parameters. The inflammatory response following burn injury may be beneficial to the immune system.

Analgesics, Opioid↗

PubMed2000

ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative group of radiotherapy of the european organization for research and treatment of cancer (EORTC).

BACKGROUND: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance. AIM: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck. METHODS: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n=10), and AF with both carbogen and nicotinamide (n=17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions. RESULTS: No significant difference in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaired when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, in an unselected group of patients. More than 20% of patients experienced grade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentages of objective response at 2 months were 81, 70 and 87%, respectively. CONCLUSION: Future ARCON trials should target selected head and neck tumor localizations and stages, and a lower nicotinamide dose is needed to reduce severe upper gastro-intestinal toxicity.

Adult↗

PubMed2000

Increased serum-soluble interleukin-2 receptor in burn patients: characterization and effects on the immune system.

The consequences of high serum concentrations of the interleukin (IL)-2 receptor alpha chain (sIL-2Ralpha) in several diseases are poorly understood. The objective of this study was to determine the form of sIL-2Ralpha in burn patients and its biological role. sIL-2Ralpha was measured in 18 severely burned individuals who received nutritional support with a normal or low fat content. sIL-2Ralpha was elevated throughout the study and it was notably lower in patients fed a low fat diet. Serum IL-6 and sIL-2Ralpha significantly correlated (r = 0.74, p < 0.05) in burn patients. The presence of sIL-2Ralpha was associated with a decrease in DR molecules in the CD2(-) and CD11b(+) cells of these patients. Western blot analysis of serum protein with N-terminal or C-terminal specific antibodies indicated that sIL-2Ralpha represents the extracellular domain of this molecule. Patient serum inhibited specifically murine, but not human IL-2-dependent T-cell proliferation. To determine the significance of sIL-2Ralpha, recombinant sIL-2Ralpha was used in different cellular model involving IL-2. sIL-2Ralpha inhibited natural killer cell activity by 50% in the presence of IL-2. The basal proliferation of peripheral blood mononuclear cells was inhibited by sIL-2Ralpha, but phytohemagglutinin-induced proliferation was unaffected by this form of receptor. Interferon (INF)-gamma production induced by OKT-3 on peripheral blood mononuclear cells was not altered by sIL-2Ralpha, but IL-2 induced increase in INF-gamma production was suppressed. The decreasing production of INF-gamma in the presence of IL-4 was significantly increased in the presence of sIL-2Ralpha in media. These results show that the large amount of sIL2-Ralpha circulating in burn patients is related to the inflammatory response. The amount of dietary fat modulates sIL2Ralpha concentration in burn patients, confirming the beneficial effect of low fat administration after burn trauma. Inhibition of T-cell activation in burn patients is not directly related to sIL-2Ralpha, although the presence of sIL-2Ralpha in serum can inhibit some IL-2 mediated response, such as the emergence of TH1 and TH2 cells.

Adolescent↗

PubMed2000

Clinical impact of dosimetry quality assurance programmes assessed by radiobiological modelling of data from the thermoluminescent dosimetry study of the European Organization for Research and Treatment of Cancer.

The European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group initiated its mailed thermoluminescence dosimetry (TLD) programme in 1986. The aim of the present study was to evaluate the clinical relevance of variations in beam output detected in the period 1993 to 1996. A total of 140 beam outputs were checked (26 for cobalt-60 units and 114 for linear accelerators) in 35 centres. Clinical dose-response data for tumour control and normal tissue morbidity were used to assess the variation in clinical outcome resulting from variability in beam output. For 75 checked beams with nominal accelerating potentials (n. a.p.) of 6 MV or less the mean ratio, +/- standard deviation (S.D.) of measured to stated output was 1.004+/-0.020. For 65 beams with n. a.p. of 8 MV or more, the ratio was 1.009+/-0.021. Even with this relatively high level of precision, broad distributions of estimated tumour control or normal tissue morbidity were found. In the 10% of the beams with the most pronounced underdosage, the loss in tumour control probability was estimated at 7-8 percentage points. Likewise, in the 10% of the beams with the most pronounced overdosage, the increase in mild/moderate morbidity was 19-22 percentage points. For severe morbidity the same beams raised the estimated incidence of severe complications from 5% to 9-10%. An estimation of the loss of uncomplicated cure probability was about 1% for both high and low energy beams. Sequential mailings considerably improved the uniformity of clinical outcome. We conclude that small deviations in beam output may lead to clinically important variations in outcome. Substantial reductions in the variation between measured and stated output can be achieved by sequential mailings. Mailed TLD checks should be an integral part of a continuously ongoing quality assurance activity in radiotherapy.

Dose-Response Relationship, Radiation↗

PubMed2000

Transfer of Ku86 RNA antisense decreases the radioresistance of human fibroblasts.

Ku86 has been shown to be involved in DNA double-strand break (DSB) repair and radiosensitivity in rodents, but its role in human cells is still under investigation. The purpose of this study was to evaluate the radiosensitivity and DSB repair after transfection of a Ku86-antisense in a human fibroblast cell line. Simian virus 40-transformed MRC5V1 human fibroblasts were transfected with a vector (pcDNA3) containing a Ku86-antisense cDNA. The main endpoints were Ku86 protein level, Ku DNA end-binding and DNA protein kinase activity, clonogenic survival, and DSB repair kinetics. After transfection of the Ku86-antisense, decreased Ku86 protein expression, Ku DNA end-binding activity, and DNA protein kinase activity were observed in the uncloned cellular population. The fibroblasts transfected with the Ku86-antisense showed also a radiosensitive phenotype, with a surviving fraction at 2 Gy of 0.29 compared with 0.75 for the control and 20% of unrepaired DSB observed at 24 hours after irradiation compared with 0% for the control. Several clones were also isolated with a decreased level of Ku86 protein, a surviving fraction at 2 Gy between 0.05 and 0.40, and 10-20% of unrepaired DSB at 24 hours. This study is the first to show the implication of Ku86 in DSB repair and in the radiosensitivity of human cells. This investigation strongly suggests that Ku86 could constitute an appealing target for combining gene therapy and radiation therapy.

Amino Acid Sequence↗

PubMed2000

Quantitative clinical radiobiology of early and late lung reactions.

PURPOSE: To quantify the response of human lung to a course of fractionated radiotherapy based on a literature review of published clinical data. MATERIALS AND METHODS: Quantitative clinical radiobiology is concerned with the estimation of parameters that describe the clinical outcome of radiotherapy as a function of patient and treatment characteristics. Here, parameters describing the steepness of the dose-response curve, the response to a change in dose per fraction and to a change in overall treatment time for early and late lung injury are compiled based on published clinical studies. RESULTS: Two phases of lung injury are seen, radiation pneumonitis and lung fibrosis. The first signs of early lung changes are seen almost immediately after irradiation. This reaction peaks after 5 to 6 months, and settles partially before 9-10 months. Around that time, the late changes become manifest and these are stable in most cases. There is an important distinction between lung injury and radiotherapy-related morbidity, as even severe changes in a small volume may not give rise to any clinical symptoms. Many assays have been developed for lung damage, and these highlight various clinical and biological aspects of lung damage. Here, the literature on steepness of dose-response curves and fractionation sensitivity is reviewed and quantified by the alpha/beta ratio of the linear-quadratic model for both radiation pneumonitis and lung fibrosis. For the early phase a significant time factor exists. Current best estimates for these radiobiological parameters are derived. Other external factors affecting these estimates are briefly discussed. CONCLUSIONS: Quantitative estimates of radiobiological characteristics of human lung are available for the pneumonitis phase where the fractionation sensitivity is in the same range as for most late-responding normal tissues. Short intensive schedules may also bear an added risk for pneumonitis as the dose recovered per day is around 0.5 Gy. For the later phase of lung fibrosis, the estimates are fewer and generally less precise. It is clear though, that the alpha/beta ratio is low, possibly 2-3 Gy. No time factor has been demonstrated for the late reaction. Due to the considerable physiological reserve capacity in the normal human lung, the relationship between damage and morbidity depends strongly on the lung volume affected. It therefore seems likely that for small volumes irradiated to high doses, the dose-limiting complications may not be due to restriction of lung function, but rather to haemorrhage and formation of fistulae.

Animals↗

PubMed2000

Tc-99m dicarboxypropane diphosphonate uptake in ovarian fibrothecoma.

A 76-year-old woman had a palpable mass in the lower abdomen. Computed tomography showed an abnormal pelvic mass with necrotic areas, probably of ovarian origin. A Tc-99m dicarboxypropane diphosphonate whole-body scan performed to evaluate the extent of the disease (i.e., the presence of bone metastases) revealed only diffuse uptake of the tracer in the pelvis. Histopathologic analysis after surgical excision of the mass revealed a fibrothecoma of the right ovary, which is a benign tumor composed of cells derived from the ovarian stroma and, in some instances, resembles the thecal element of the follicle.

Aged↗

PubMed2000

Immune function of bovine leukocytes after in vitro exposure to selected heavy metals.

OBJECTIVE: To study effects of in vitro exposure of bovine leukocytes to mercury, cadmium, and lead on phagocytosis, natural killer cell activity, and lymphocyte proliferation. SAMPLE POPULATION: Leukocytes from 6 nonpregnant Holstein heifers. PROCEDURE: Leukocytes were exposed in vitro to the aforementioned metals, and leukocyte functions were assessed. RESULTS: Phagocytosis was suppressed by 10(-5) to 10(-7) M CdCl2 and by 10(-5) and 10(-6) M HgCl2, but not 10(-7) M HgCl2 nor 10(-4) to 10(-6) M PbCl2. Spontaneous and concanavalin A- or phytohemagglutinin-stimulated proliferation of metal-treated bovine blood mononuclear cells was not significantly different from that of nontreated control cells, except for enhanced spontaneous proliferation in response to 10(-5) M HgCl2. When proliferation was expressed as a stimulation index, a dose-dependent increase of spontaneous proliferation was observed in response to exposure to HgCl2 and PbCl2. Compared with response to 10(-6) or 10(-7) M CdCl2, reduction of mitogen-induced and spontaneous proliferation was observed on exposure to 10(-5) M CdCl2. Natural killer cell activity against YAC-1 target cells, evaluated by flow cytometry, was decreased only in cells exposed to 10 M HgCl2. CONCLUSION AND CLINICAL RELEVANCE: Bovine leukocytes are susceptible to the immunomodulatory effects of in vitro exposure to heavy metals at concentrations equal to or higher than those at which similar effects are seen for leukocytes from most other animal species for which data are available for comparison. Exception is phagocytosis, which is severely affected by low concentrations of CdCl2 and HgCl2 in cattle. Reduction of defense mechanisms on exposure to metals could lead to increased susceptibility to potential pathogens.

Animals↗

PubMed1999

Critical appraisal of a conformal head and neck cancer irradiation avoiding electron beams and field matching.

PURPOSE: In head and neck cancer patients, spinal chains are usually irradiated by a combination of photon and electron beams, requiring high precision in field matching. This study compares a conventional treatment approach where two lateral photon beams are combined to direct electron fields, to a conformal radiotherapy based on five photon fields, covering the whole neck. METHODS AND MATERIALS: A comparative analysis of dose distributions and dose-volume histograms was carried out in patients with locally advanced head and neck tumors, for which planning target volumes (PTV) were outlined from the base of the skull down to the supraclavicular region. The prescribed dose to PTV (excluding booster irradiation) was 54 Gy, with spinal dose constraint not exceeding 75% of the total dose, whatever the technique. RESULTS: For the new five-field technique, minimum and maximum point doses showed mean deviations, on five patients entered in the study, of 84% and 113% from the ICRU prescription point. In the conventional treatment, the corresponding figures were 73% and 112%, respectively. A positioning error analysis (isocenter displacement of 2 mm, in all directions) did not elicit any systematic difference in five-field treatment plans while hot spots were found with electron fields. CONCLUSIONS: The five-field technique appears routinely feasible and compares favorably with the conventional mixed photon- and electron-therapy approach, especially in regard to its better compliance with dose homogeneity requirements and a reduced risk in dose inhomogeneity related to field matching and patient positioning.

Brain↗

PubMed1999

ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC.

BACKGROUND: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.

Administration, Inhalation↗

PubMed1999

Differential toxicity of anticancer drugs on late (GM-CFC) and early (LTC-IC) hemopoietic progenitors in vitro.

The clinical hematological toxicity of cytotoxic drugs can be acute, with a nadir of neutrophil count after 2 weeks and recovery the following week, or subacute, with a nadir of neutrophil count after 3 weeks and recovery in the following 2-3 weeks. The explanation usually given for this difference is that drugs in the first group are more toxic to mature hemopoietic precursors, while drugs of the second type are more toxic to undifferentiated cells. In an attempt to verify this hypothesis, we compared in vitro the effect of toxic doses of etoposide and tallimustine as representatives of drugs with acute toxicity, and of BCNU, melphalan, and carzelesin as representatives of drugs with subacute toxicity. Their effects were studied separately on more differentiated and earlier progenitors represented by granulocyte-macrophage colony-forming cells (GM-CFC) and long-term culture-initiating cells (LTC-IC), respectively. Etoposide, melphalan, BCNU, and carzelesin showed higher toxicity in differentiated than in early precursors: the concentration of drug inhibiting 70% (ID70) of GM-CFC inhibited only by 10-40% the growth of LTC-IC. Tallimustine, in contrast, inhibited both GM-CFC and LTC-IC at comparable levels. These results do not correspond to the clinical pattern of myelotoxicity observed for those drugs. We conclude that the differential effects of antitumor drugs on later (GM-CFC) or earlier (LTC-IC) hemopoietic precursors may not represent a valid model for the pattern of myelotoxicity observed in humans.

Animals↗

PubMed1999

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Actuarial Analysis↗

PubMed1999

Accelerated radiotherapy, carbogen, and nicotinamide in glioblastoma multiforme: report of European Organization for Research and Treatment of Cancer trial 22933.

PURPOSE: A three-step phase I/II trial associating accelerated radiotherapy with carbogen (step 1, ARCO), with nicotinamide (step 2, ARN), or with both (step 3, ARCON) was conducted, the aim of which was to overcome the effects of proliferation and hypoxia as potential causes of tumor radioresistance in glioblastoma multiforme. PATIENTS AND METHODS: Radiotherapy consisted of 60 Gy delivered over 4 weeks in 1.5-Gy fractions twice daily, 5 days a week. Carbogen breathing was started 5 minutes before each fraction and continued until the end of each treatment session. Nicotinamide was given daily as a single oral dose of 85 mg/kg. RESULTS: A total of 115 patients with a median age of 55 years were registered. Of 107 eligible patients, 23 were registered in step 1, 28 in step 2, and 56 in step 3. The planned treatment was administered without any interruption in 72% of patients (86% in ARCO but 68% in ARN and ARCON). The incidence and severity of acute skin and mucous membrane toxicity were higher in patients who received nicotinamide (ie, the ARN and ARCON groups). Grade 1 to 2 gastrointestinal toxicity was observed in 44% of patients in the ARN group and 32% of patients in the ARCON group, but only in 8% of patients in the ARCO group. Eight percent of evaluated patients presented with abnormal liver test results at treatment completion. The dose of corticosteroids had to be increased in 44% of patients. Late neurologic side effects were similar in all treatment steps and were observed mostly in patients with disease progression. Median survival times for patients treated with ARCO, ARN, and ARCON were 10.1, 9.7, and 11.1 months, respectively. CONCLUSION: Feasibility of ARCO treatment was good but that of ARN and ARCON was only fair. This probably reflected the higher acute toxicity rate, particularly gastrointestinal, for patients receiving nicotinamide. The dose of corticosteroids had to be increased frequently during treatment, suggesting a higher than expected acute neurologic toxicity. Overall survival was similar in the three treatment steps and not different when compared with results of other series that used radiotherapy alone.

Administration, Inhalation↗

PubMed1999

Fractures.

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Child↗