Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Radiat Oncol ; 15(1): 253, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138837

RESUMO

BACKGROUND: The ESCALOX trial was designed as a multicenter, randomized prospective dose escalation study for head and neck cancer. Therefore, feasibility of treatment planning via different treatment planning systems (TPS) and radiotherapy (RT) techniques is essential. We hypothesized the comparability of dose distributions for simultaneous integrated boost (SIB) volumes respecting the constraints by different TPS and RT techniques. METHODS: CT data sets of the first six patients (all male, mean age: 61.3 years) of the pre-study (up to 77 Gy) were used for comparison of IMRT, VMAT, and helical tomotherapy (HT). Oropharynx was the primary tumor location. Normalization of the three step SIB (77 Gy, 70 Gy, 56 Gy) was D95% = 77 Gy. Coverage (CVF), healthy tissue conformity index (HTCI), conformation number (CN), and dose homogeneity (HI) were compared for PTVs and conformation index (COIN) for parotids. RESULTS: All RT techniques achieved good coverage. For SIB77Gy, CVF was best for IMRT and VMAT, HT achieved highest CN followed by VMAT and IMRT. HT reached good HTCI value, and HI compared to both other techniques. For SIB70Gy, CVF was best by IMRT. HTCI favored HT, consequently CN as well. HI was slightly better for HT. For SIB56Gy, CVF resulted comparably. Conformity favors VMAT as seen by HTCI and CN. Dmean of ipsilateral and contralateral parotids favor HT. CONCLUSION: Different TPS for dose escalation reliably achieved high plan quality. Despite the very good results of HT planning for coverage, conformity, and homogeneity, the TPS also achieved acceptable results for IMRT and VMAT. Trial registration ClinicalTrials.gov Identifier: NCT01212354, EudraCT-No.: 2010-021139-15. ARO: ARO 14-01.

2.
PLoS One ; 15(9): e0237501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877418

RESUMO

PURPOSE: The concept of dysphagia/aspiration-related structures (DARS) was developed against the background of severe late side effects of radiotherapy (RT) for head and neck cancer (HNC). DARS can be delineated on CT scans, but with a better morphological discrimination on magnetic resonance imaging (MRI). Swallowing function was analyzed by use of patient charts and prospective investigations and questionnaires. METHOD: Seventeen HNC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy between 5/2012 - 8/2015 were included. Planning CT (computed tomography) scans and MRIs (magnetic resonance imaging) prior, during 40 Gray (Gy) radiotherapy and posttreatment were available and co-registered to delineate DARS. The RT dose of each DARS was calculated. Five patients were investigated posttreatment for swallowing function and assessed by means of various questionnaires for quality of life (QoL), swallowing, and voice function. RESULTS: By retrospective comparison of DARS volume, a significant change in four of eight DARS was detected over time. Three increased and one diminished. The risk of posttreatment dysphagia rose by every 1Gy above the mean dose (D mean) of RT to DARS. 7.5 was the risk factor for dysphagia in the first 6 months, reducing to 4.7 for months 6-12 posttreatment. For all five patients of the prospective part of swallowing investigations, a function disturbance was detected. These results were in contrast to the self-assessment of patients by questionnaires. There was neither a dose dependency of D mean DARS volume changes over time nor of dysphonia and no correlation between volume changes, dysphagia or dysphonia. CONCLUSION: Delineation of DARS on MRI co-registered to planning CT gave the opportunity to differentiate morphology better than by CT alone. Due to the small number of patients with complete MRI scans over time, we failed to detect a dose dependency of DARS and swallowing and voice disorder posttreatment.


Assuntos
Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/radioterapia , Imagem por Ressonância Magnética , Sucção , Tomografia Computadorizada por Raios X , Adulto , Idoso , Deglutição , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Voz , Adulto Jovem
3.
Radiat Oncol ; 14(1): 66, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992022

RESUMO

BACKGROUND: Multimodal treatment with neoadjuvant chemoradiation followed by surgery (nCRT + S) is the treatment of choice for patients with locally advanced or node-positive esophageal squamous cell carcinoma (E-SCC). Those who are unsuitable or who decline surgery can be treated with definitive chemoradiation (dCRT). This study compares the oncologic outcome of nCRT + S and dCRT in E-SCC patients. METHODS: Between 2011 and 2017, 95 patients with E-SCC were scheduled for dCRT or nCRT+ S with IMRT at our department. Patients undergoing dCRT received at least 50 Gy and those undergoing nCRT + S received at least 41.4 Gy. All patients received simultaneous chemotherapy with either carboplatin and paclitaxel or cisplatin and 5-fluoruracil. We retrospectively compared baseline characteristics and oncologic outcome including overall survival (OS), progression-free survival (PFS) and site of failure between both treatment groups. RESULTS: Patients undergoing dCRT were less likely to have clinically suspected lymph node metastases (85% vs. 100%, p = 0.019) than patients undergoing nCRT + S and had more proximally located tumors (median distance from dental arch to cranial tumor border 20 cm vs. 26 cm, p < 0.001). After a median follow up of 25.6 months for surviving patients, no significant differences for OS and PFS were noticed comparing nCRT + S and dCRT. However, the rate of local tumor recurrence was significantly higher in patients treated with dCRT than in those treated with nCRT + S (38% vs. 10%, p = 0.002). Within a multivariate Cox regression model, age, tumor location, and tumor grading were the only independent parameters affecting OS and PFS. In addition to that, proximal tumor location was the only parameter independently associated with an increased risk for local treatment failure. CONCLUSION: In E-SCC patients treated with either dCRT or nCRT + S, a higher rate of local tumor recurrence was seen in patients treated with dCRT than in patients treated with nCRT + S. There was at least a trend towards an improved OS and PFS in patients undergoing nCRT + S. However, this should be interpreted with caution, because proximal tumor location was the only parameter independently affecting the risk of local tumor recurrence.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/mortalidade , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Strahlenther Onkol ; 195(6): 475-481, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30523417

RESUMO

BACKGROUND: The goal of this study was to investigate if daily dose recalculations are necessary or if less time-consuming approaches can be used to identify dose differences to the planned dose in patients with head and neck cancers (H&N). METHODS: For 12 H&N patients treated with helical tomotherapy, daily dose calculations were performed retrospectively. Four different summation doses (SuDo) were calculated: DayDo (daily dose calculation), MVCTx2, MVCTx5, and MVCTx10 (dose calculations every second, fifth, and tenth fraction). Dose recalculations were depicted on the last contoured mega voltage CT (MVCT). The DayDo was compared to the planned dose and to the less time-consuming SuDo scenarios. The doses were assessed for the planning target volume (PTV) and the organs at risk (OARs): mandible (mand), spinal cord (SC), spinal cord +5 mm (SC+5 mm), parotid glands (PG). RESULTS: The ipsilateral PG, contralateral PG, and PTV volume decreased by -22.5% (range: -34.8 to 5.2%), -19.5% (-31.5 to 15.8%), and -2.6% (-16.7 to 0.2%), respectively. There was a significant median mean dose (Dmean) dose difference for DayDo compared to the planned dose for PG total of 1.9 Gy (-3.3 to 7.3 Gy). But less time-consuming SuDo compared to DayDo showed statistically significant but not clinically relevant (<2%) dose differences for several organs. Hence the small dose difference to the gold standard (DayDo), we recommend dose recalculations every fifth MVCT in order to identify the occurrence of dose differences compared to the planned dose. CONCLUSION: Daily dose calculations are the most precise to assess dose differences between actual and planned dose. Dose recalculations on every fifth MVCT (i. e., weekly control CTs) are an applicable and time-saving way of identifying patients with significant dose differences compared to the planned dose.


Assuntos
Neoplasias Otorrinolaringológicas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Fatores de Tempo
5.
Radiat Oncol ; 13(1): 139, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30068371

RESUMO

BACKGROUND: While neoadjuvant chemoradiation therapy (nCRT) with subsequent surgery is the treatment of choice for patients with locally advanced or node-positive squamous cell carcinoma of the esophagus (SCC) suitable for surgery, patients who are unsuitable for surgery or who refuse surgery should be treated with definite chemoradiation therapy (dCRT). Purpose of this study was to compare toxicity and oncologic outcome of dCRT with either cisplatin and 5-fluoruracil (CDDP/5FU) or carboplatin and paclitaxel (Carb/TAX) in patients with SCC. METHODS: Twenty-two patients who received dCRT with carboplatin (AUC2, weekly) and paclitaxel (50 mg per square meter of body-surface area, weekly) were retrospectively compared to 25 patients who were scheduled for dCRT with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1-5 and day 29-33. For the per-protocol (PP) analysis, PP treatment was defined as complete radiation therapy with at least 54Gy and at least three complete cycles of Carb/TAX or complete radiation therapy with at least 54Gy and at least one complete cycle of CDDP/5FU. While patients who were scheduled for dCRT with Carb/TAX received a significantly higher total radiation dose (median dose 59.4Gy vs. 54Gy, p < 0.001) than patients who were scheduled for dCRT with CDDP/5FU, no significant differences were seen for other parameters (age, sex, TNM-stage, grading and tumor extension). RESULTS: Forty-seven patients (25 patients treated with CDDP/5FU and 22 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 41 of 47 patients (23 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. Severe myelotoxicity (≥ III°) was seen in 52% (CDDP/5FU) and 55% of patients (Carb/TAX), respectively (p = 1.000). In the univariate binary logistic regression analysis, patients age was the only factor associated with an increased risk of ≥ III° myelotoxicity (hazard ratio 1.145, 95% CI 1.035; 1.266; p = 0.009). Regarding treatment efficiency, no significant differences were seen for overall survival (OS) and freedom from relapse (FFR) between both treatment groups. CONCLUSION: Myelotoxicity and oncologic outcome under dCRT were not different for patients with SCC of the esophagus treated with either CDDP/5FU or Carb/TAX. The putative equivalence of dCRT with Carb/TAX in this setting should be further investigated in prospective trials. However, our data reveal that the risk of significant myelotoxicity increases with patient age and therefore other chemotherapy regimens might be evaluated in elderly patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Superfície Corporal , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Estudos Prospectivos , Estudos Retrospectivos
6.
Radiat Oncol ; 12(1): 182, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29157271

RESUMO

PURPOSE: Neoadjuvant chemoradiation (nCRT) is the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC). Today radiation oncologists can choose between two different therapy regimes including chemoradiation with cisplatin and 5-fluoruracil (CDDP/5FU) and chemoradiation analogue to the CROSS-regime with carboplatin and paclitaxel (Carb/TAX). However, there is a lack of studies comparing these regimes, especially for the subgroup of patients with SCC. In this study, we want to compare nCRT with CDDP/5FU and nCRT with Carb/TAX for patients with locally advanced SCC. PATIENTS AND METHODS: We retrospectively compared 20 patients who were scheduled for nCRT with a total radiation dose of 41.4 Gy (daily dose of 1.8 Gy) and weekly chemotherapy with carboplatin (Area under the curve 2) and Paclitaxel (50 mg per square meter of body-surface area) according to the CROSS-regime to 31 patients who were scheduled for nCRT with a total radiation dose of 45 Gy (daily dose of 1.8 Gy) and simultaneous chemotherapy with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1-5 and day 29-33. For the per-protocol (PP) analysis, per protocol treatment was defined as either complete radiation with 41.4 Gy, at least three complete cycles of Carb/TAX and subsequent surgery or complete radiation with 45 Gy, at least one complete cycle of CDDP/5FU and subsequent surgery. RESULTS: Fifty-one patients (31 patients treated with CDDP/5FU and 20 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 44 patients (26 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. No significant differences were seen for baseline and tumor characteristics like age, sex, TNM-stage, grading and tumor extension between patients treated with Carb/TAX and patients treated with CDDP/5FU. The most common tumor regression grade after nCRT was grade I as classified by Becker et al., which was observed in 84 and 79% of patients. No significant differences in tumor regression grades were seen between both regimes. Postoperative insufficiency of the anastomosis was seen in 6 patients (33%) who were treated with Carb/TAX and 4 patients (15%) who were treated with CDDP/5FU (p = 0.273). Patients treated with CDDP/5FU developed significantly more cumulative hematologic III° (CTCAE) toxicities (58% vs 20%; p = 0.010) than patients treated with Carb/TAX. In contrast to that, there was no significant difference for overall survival (OS) and freedom from relapse (FFR) between treatment groups. CONCLUSION: In this retrospective analysis, no significant difference was seen for OS and FFR between nCRT with CDDP/5FU and nCRT with Carb/TAX. However, the application of CDDP/5FU was associated with significantly more hematologic III°- toxicities compared to Carb/TAX. Future prospective trials should investigate if these results are reproducible in randomized patient cohorts.


Assuntos
Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/administração & dosagem , Paclitaxel/administração & dosagem , Idoso , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento
7.
Radiat Oncol ; 12(1): 45, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28249612

RESUMO

BACKGROUND: Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation. METHODS: The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start. DISCUSSION: The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Hipóxia Tumoral , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida , Adulto Jovem
8.
Radiat Oncol ; 11(1): 133, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27716349

RESUMO

BACKGROUND: Especially elderly and frail patients have a limited ability to compensate for side effects of a radical treatment of head and neck malignancies. Limiting the target volume to the macroscopic disease, without prophylactic nodal irradiation, might present a feasible approach for these patients. The present work therefore aims evaluating an IMRT/IGRT -SIB concept for safety and efficacy. METHODS: The study retrospectively enrolled 27 patients with head and neck cancers treated between 01/2012 and 05/2015. We evaluated patient files for clinical status, concomitant diseases, treatment side, and treatment volumes as well as for side effects and tumor responses. To describe efficacy and risk factors for worse outcome and higher grade toxicities, we performed cox regression analysis as well as Kaplan-Meier survival time analysis. RESULTS: Median survival was 181 days, 75 % patients showed an early local response at six weeks of follow up. Most patients developed mild to moderate acute toxicities, only one patient with grade IV mucositis was seen. The grade of toxicities was correlated to the size of the PTV. Concomitant diseases, metastatic disease, and G3 Grading were indicators for worse prognosis. CONCLUSION: The IMRT/IGRT SIB concept is a safe and feasible radiotherapy concept for patients not able or not willing to undergo radical treatment.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Modelos de Riscos Proporcionais , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
9.
Strahlenther Onkol ; 184(3): 169-74, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18330514

RESUMO

PURPOSE: To investigate the relationship between the hypoxia-inducible factor-(HIF-)1alpha expression in tumor tissue, tumor oxygenation and hemoglobin levels in patients with advanced cervical cancers prior to radiotherapy and the effect on clinical outcome. PATIENTS AND METHODS: The investigation included 44 patients who underwent definitive radiotherapy for advanced cervical cancers between May 1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1alpha expression was determined by immunohistochemistry. In the same tumor area, tumor tissue oxygenation (pO2) was measured using the Eppendorf device. RESULTS: The 5-year cancer-specific survival of all patients was 60%. Twelve of 44 tumor specimens were HIF-1alpha-negative with a significantly better 5-year survival (92 +/- 8%) versus 32 patients who were HIF-1alpha-positive (45 +/- 10%; p < 0.02). There was no correlation between HIF-1alpha expression and tumor oxygenation (p = 0.57 both for pO2 median and hypoxic fraction < 5 mmHg vs. HIF-1alpha expression). However, patients with hemoglobin levels < 11 g/dl showed elevated HIF-1alpha expression compared to patients with hemoglobin levels > 12.5 g/dl (p = 0.04). Furthermore, HIF-1alpha correlated with vascular endothelial growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF-1alpha expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk of tumor-related death. CONCLUSION: The study indicates, that endogenous tumor markers such as HIF-1alpha may serve as prognostic markers of clinical outcome concerning cervical cancer after primary radiotherapy.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Biomarcadores Tumorais , Biópsia , Braquiterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Interpretação Estatística de Dados , Feminino , Hemoglobinas/análise , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxigênio/metabolismo , Aceleradores de Partículas , Polarografia , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Risco , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Strahlenther Onkol ; 179(7): 493-8, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12835887

RESUMO

BACKGROUND: Amifostine is a radioprotective drug applied to reduce acute radiation toxicity during a course of conventionally fractionated radiotherapy. In the present study, amifostine was used in patients undergoing adjuvant radiochemotherapy for rectal cancer. It was described previously that additional application of amifostine led to less acute skin and bowel toxicity. The present study was aimed to determine whether amifostine has an influence on the amount of residual chromosomal damage. MATERIAL AND METHODS: Peripheral lymphocytes of twelve rectal cancer patients who had undergone postoperative radiochemotherapy 2-3 years ago were investigated for residual chromosomal damage using 24-color fluorescence in situ hybridization (24-color FISH). All twelve patients had received a total dose of 55.8 Gy in conventional fractionation of 1.8 Gy and a 120-h continuous infusion of 5-fluorouracil (5-FU) chemotherapy (1,000 mg/m(2) per day) in the 1st and 5th week of irradiation. Seven out of twelve patients had been given additional amifostine on chemotherapy days (500 mg total dose as short i.v. infusion immediately prior to the daily radiation fraction). Cultivation of lymphocytes and 24-color FISH were performed according to standard protocols. 100 metaphases per patient were analyzed for chromosomal aberrations in a blind study. RESULTS: Analysis of the average number of breaks per mitosis (B/M) revealed an increased amount of residual chromosomal damage in the group treated with amifostine (0.65 B/M [0.32-0.97]) as well as in those treated without amifostine (0.76 B/M [0.31-1.25]). Also the average number of cells containing aberrations per 100 analyzed metaphases was similar (with amifostine: 22.1 [13-32] vs. 24.4 [13-35] without amifostine). The aberration types, occurring as simple translocations, reciprocal translocations, breaks, dicentrics, inversions, rings and complex chromosomal rearrangements, did not show any specific accumulation in one or the other group either. CONCLUSION: While there was a significant amifostine-mediated clinical amelioration of normal tissue toxicity, the comparison of residual chromosomal damage 2-3 years after completion of radiochemotherapy was characterized by a high interindividual variation, and no equivalent difference could be detected between the two groups.


Assuntos
Amifostina/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Aberrações Cromossômicas , Coloração Cromossômica , Dano ao DNA/efeitos da radiação , Fluoruracila/efeitos adversos , Protetores contra Radiação/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Idoso , Amifostina/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Infusões Intravenosas , Linfócitos , Masculino , Pessoa de Meia-Idade , Protetores contra Radiação/efeitos adversos , Radioterapia Adjuvante , Neoplasias Retais/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA