RESUMEN
PURPOSE: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m(2) (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. RESULTS: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. CONCLUSIONS: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.
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Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Cisplatino/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Quinazolinas/efectos adversos , Adulto , Anciano , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Esquema de Medicación , Estudios de Factibilidad , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Quinazolinas/administración & dosificaciónRESUMEN
BACKGROUND AND PURPOSE: Only sparse reports have been made about radiation exposure of the treating physician during prostate seed implantation. Therefore, thermoluminescence dosimeter (TLD) measurements on the index fingers and the backs of both hands were conducted. MATERIAL AND METHODS: Stranded iodine-125 seeds with a mean apparent activity of 27.4 MBq per seed were used. During application, the treating physician manipulated the loaded needle with the index fingers, partially under fluoroscopic control. Four physicians with varying experience treated 24 patients. The radiation exposure was determined with TLD-100 chips attached to the index fingertips and the backs of hands. Radiation exposure was correlated with the physician's experience. RESULTS: The average brachytherapy duration by the most experienced physician was 19.2 min (standard deviation sigma = 1.2 min; novices: 34.8 min [sigma = 10.2 min]). The mean activity was 1,703 MBq (sigma = 123 MBq), applied with 16.3 needles (sigma = 2.5 needles; novices: 1,469 MBq [sigma = 229 MBq]; 16.8 needles [sigma = 2.3 needles]). The exposure of the finger of the "active hand" and the back of the hand amounted to 1.31 mSv (sigma = 0.54 mSv) and 0.61 mSv (sigma = 0.23 mSv), respectively (novices: 2.07 mSv [sigma = 0.86 mSv] and 1.05 mSv [sigma = 0.53 mSv]). CONCLUSION: If no other radiation exposure needs to be considered, an experienced physician can perform about 400 applications per year without exceeding the limit of 500 mSv/year; for novices, the corresponding figure is about 200.
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Braquiterapia , Dedos/efectos de la radiación , Mano/efectos de la radiación , Radioisótopos de Yodo/uso terapéutico , Exposición Profesional , Neoplasias de la Próstata/radioterapia , Dosimetría Termoluminiscente , Carga Corporal (Radioterapia) , Humanos , Radioisótopos de Yodo/efectos adversos , Masculino , Estadificación de Neoplasias , Enfermedades Profesionales/prevención & control , Neoplasias de la Próstata/patología , Traumatismos por Radiación/prevención & control , Protección RadiológicaRESUMEN
OBJECTIVE: To evaluate quality of life (QOL) after radical retropubic prostatectomy (RP) and low-dose-rate brachytherapy (BT). METHODS: Between 2001 and 2004, RP or BT was performed in 212 patients. QOL data were evaluated with the European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0, the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 questionnaires. QOL data were compared. RESULTS: RP and BT were performed in 142 and 70 patients, respectively. The mean follow-up was 24 months (5-53). The mean overall global health score for patients after RP was 78 (0-100) and after BT it was 83 (33-100), and it showed a trend in favour of BT. The follow-up lasted at most 53 months, and the period was divided into yearly categories. Patients who underwent BT showed worse global health in the first year after operation, but thereafter they showed better health. Patients who received BT showed a trend towards having lower functional-scale and symptom-scale scores in the first year after operation, and then higher scores for any subsequent year of follow-up. Only diarrhoea was temporarily worse in the second year after BT compared to RP. The mean total IPSS and QOL score for BT and RP patients during follow-up showed no significant difference. CONCLUSION: Patients treated with BT or RP have similar QOL scores. QOL after BT is worse in the first year after treatment, but thereafter it is better than QOL after RP.
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Braquiterapia , Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Calidad de Vida , Anciano , Braquiterapia/efectos adversos , Bases de Datos como Asunto , Diarrea/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Dosis de Radiación , Encuestas y Cuestionarios , Suiza , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours. PATIENTS AND METHODS: One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed. RESULTS: The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis. CONCLUSION: Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients.
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Fibromatosis Agresiva/radioterapia , Fibromatosis Agresiva/cirugía , Radioterapia/métodos , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Niño , Preescolar , Terapia Combinada , Supervivencia sin Enfermedad , Europa (Continente) , Humanos , Lactante , Persona de Mediana Edad , Recurrencia , Factores de TiempoRESUMEN
Owing to their sessile nature, plants are constantly exposed to a multitude of environmental stresses to which they react with a battery of responses. The result is plant tolerance to conditions such as excessive or inadequate light, water, salt and temperature, and resistance to pathogens. Not only is plant physiology known to change under abiotic or biotic stress, but changes in the genome have also been identified. However, it was not determined whether plants from successive generations of the original, stressed plants inherited the capacity for genomic change. Here we show that in Arabidopsis thaliana plants treated with short-wavelength radiation (ultraviolet-C) or flagellin (an elicitor of plant defences), somatic homologous recombination of a transgenic reporter is increased in the treated population and these increased levels of homologous recombination persist in the subsequent, untreated generations. The epigenetic trait of enhanced homologous recombination could be transmitted through both the maternal and the paternal crossing partner, and proved to be dominant. The increase of the hyper-recombination state in generations subsequent to the treated generation was independent of the presence of the transgenic allele (the recombination substrate under consideration) in the treated plant. We conclude that environmental factors lead to increased genomic flexibility even in successive, untreated generations, and may increase the potential for adaptation.
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Aclimatación/efectos de los fármacos , Aclimatación/efectos de la radiación , Arabidopsis/efectos de los fármacos , Arabidopsis/efectos de la radiación , Epigénesis Genética , Recombinación Genética/efectos de los fármacos , Recombinación Genética/efectos de la radiación , Alelos , Arabidopsis/genética , Arabidopsis/fisiología , Cruzamientos Genéticos , Flagelina/farmacología , Luz , Plantas Modificadas Genéticamente , Polen/fisiología , Recombinación Genética/genética , Recombinación Genética/fisiología , Transgenes/genética , Rayos UltravioletaRESUMEN
Intermolecular recombination events were monitored in Arabidopsis thaliana lines using specially designed recombination traps consisting of tandem disrupted beta-glucuronidase or luciferase reporter genes in direct repeat orientation. Recombination frequencies (RFs) varied between the different lines, indicating possible position effects influencing intermolecular recombination processes. The RFs between sister chromatids and between homologous chromosomes were measured in plants either hemizygous or homozygous for a transgene locus. The RFs in homozygous plants exceeded those of hemizygous plants by a factor of >2, implying that in somatic plant cells both sister chromatid recombination and recombination between homologous chromosomes exist for recombinational DNA repair. In addition, different DNA-damaging agents stimulated recombination in homozygous and hemizygous plants to different extents in a manner dependent on the type of DNA damage and on the genomic region. The genetic and molecular analysis of recombination events showed that most of the somatic recombination events result from gene conversion, although a pop-out event has also been characterized.
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Arabidopsis/genética , Cromátides/genética , Recombinación Genética/genética , Bleomicina/farmacología , Cromosomas de las Plantas/genética , Daño del ADN , Reparación del ADN , ADN de Plantas/efectos de los fármacos , ADN de Plantas/genética , ADN de Plantas/efectos de la radiación , Genes Reporteros/genética , Glucuronidasa/genética , Glucuronidasa/metabolismo , Homocigoto , Luciferasas/genética , Luciferasas/metabolismo , Metilmetanosulfonato/farmacología , Plantas Modificadas Genéticamente , Rayos UltravioletaRESUMEN
PURPOSE: To report results of 18-month follow up of external beam radiation therapy with photons for subfoveal classic or occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). DESIGN: Randomized clinical trial. METHODS: A total of 161 patients with subfoveal CNV in ARMD were recruited in a prospective double-masked study. The posterior pole of the afflicted eye was given 1 Gy (4 x 0.25 Gy) in the control group and 8 Gy (4 x 2 Gy) or 16 Gy (4 x 4 Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV size were measured. RESULTS: At the completion of the study 150 (93.2%), 139 (86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months, respectively. The mean number of lines lost in the BCVA was -1.69, -2.2, and -3.23 in the 1 Gy group; -0.94, -1.25, and -1.73 in the 8 Gy group; -0.51, -0.67, and -1.93 in the 16 Gy group. The difference was significant after 12 months (P =.016 for 8 Gy vs. 1 Gy; P =.006 for 16 Gy vs. 1 Gy), and 18 months (P =.011 for 8 Gy vs. 1 Gy; P =.05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with an initial distance visual acuity >or=20/100, benefited more from treatment. A significant difference was not found between control group and treatment groups in the reading ability and in the CNV size. No radiation-associated side effects were reported thus far. CONCLUSION: The number of lines lost in the BCVA was less in the 8 Gy and 16 Gy treatment groups than in the control group during the complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without showing any difference in efficacy, resulted in a near stabilization of the BCVA in patients with subfoveal classic or occult CNV in ARMD. Further studies are necessary to determine the significance of repeated radiotherapy series with a dose of 8 Gy to improve the effect on the CNV size and thereby to prolong stabilization of distance visual acuity.