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OBJECTIVE: To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. METHODS: Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. RESULTS: The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95%CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95%CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. CONCLUSIONS: Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence in adolescents increased significantly over the whole period 1983-2007. Several specific tumour groups showed significant rises or decrements in childhood or adolescence, although the small number of cases precludes showing significant trends or inflexion points.
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BACKGROUND: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups. RESULTS: Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05). CONCLUSION: In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term. IMPACT: As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted.
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Factor I del Crecimiento Similar a la Insulina/análisis , Neoplasias de la Próstata/etiología , Anciano , Estudios de Casos y Controles , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/sangre , RiesgoRESUMEN
BACKGROUND: The evidence about nitrosamines and heme iron intake and cancer risk is limited, despite the biologic plausibility of the hypothesis that these factors might increase cancer risk. We investigated the association between dietary nitrosamines and heme iron and the risk of prostate cancer among participants of European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Data on food consumption and complete follow-up for cancer occurrence was available for 139,005 men, recruited in 8 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, and study center, and adjusted for total energy intake, smoking status, marital status, dairy products, educational level, and body mass index. RESULTS: After a mean follow-up of 10 years, 4,606 participants were diagnosed with first incident prostate cancer. There was no overall association between prostate cancer risk and nitrosamines exposure (preformed and endogenous) or heme iron intake (HR for a doubling of intake: 1.00; 95% CI: 0.98-1.03 for N-Nitrosodimethlyamine, 0.95; 95% CI: 0.88-1.03 for endogenous Nitrosocompounds, and 1.00; 95 CI: 0.97-1.03 for heme iron). CONCLUSIONS AND IMPACT: Our findings do not support an effect of nitrosamines (endogenous and exogenous) and heme iron intake on prostate cancer risk.
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Hemo/metabolismo , Hierro de la Dieta/efectos adversos , Recurrencia Local de Neoplasia/etiología , Nitrosaminas/efectos adversos , Neoplasias de la Próstata/etiología , Anciano , Europa (Continente)/epidemiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata/epidemiología , Factores de RiesgoRESUMEN
This systematic review determines the benefit of treatment with Ginkgo biloba (Ginkgo) in Alzheimer's disease (AD) concerning patient-relevant outcomes. Bibliographic databases, clinical trial and study result registries were searched for randomized controlled trials (RCTs) in patients with AD (follow-up ≥16 weeks) comparing Ginkgo to placebo or a different treatment option. Manufacturers were asked to provide unpublished data. If feasible, data were pooled by meta-analysis. Six studies were eligible; overall, high heterogeneity was shown for most outcomes, except safety aspects. Among studies administering high-dose Ginkgo (240 mg), all studies favour treatment though effects remain heterogeneous. In this subgroup, a benefit of Ginkgo exists for activities of daily living. Cognition and accompanying psychopathological symptoms show an indication of a benefit. A harm of Ginkgo is not evident. An estimation of the effect size was not possible for any outcome. Further evidence is needed which focuses especially on subgroups of AD patients.
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Enfermedad de Alzheimer/tratamiento farmacológico , Nootrópicos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Relación Dosis-Respuesta a Droga , Ginkgo biloba , Humanos , Nootrópicos/efectos adversos , Extractos Vegetales/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study. METHODS: After a mean follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables. RESULTS: With increasing variety in vegetable subgroups, risk of lung cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97). CONCLUSION: Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers. IMPACT: Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk.
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Dieta , Neoplasias Pulmonares/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/prevención & control , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Frutas , Humanos , Incidencia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , VerdurasRESUMEN
Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.
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Estado Nutricional , Neoplasias de la Próstata/epidemiología , Vitamina D/análogos & derivados , Anciano , Estudios de Casos y Controles , Intervalos de Confianza , Europa (Continente)/epidemiología , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Oportunidad Relativa , Estudios Prospectivos , Neoplasias de la Próstata/sangre , Medición de Riesgo , Factores de Riesgo , Estaciones del Año , Encuestas y Cuestionarios , Reino Unido/epidemiología , Vitamina D/sangreRESUMEN
BACKGROUND: We previously demonstrated that a mathematical technique called recursive partitioning analysis (RPA), when applied to the Radiation Therapy Oncology Group Head and Neck Cancer database, created rules that formed subgroups ("classes") having unique outcomes. We sought to learn if the application of RPA-derived rules to a new head and neck database would create classes that were similarly associated with outcome and thereby validate this technique. METHODS: The rules derived from recursive partitioning analysis of the previous database were used to subgroup an independent, new head and neck cancer database (RTOG 85-27), created as part of a phase III trial of the hypoxic-cell radiosensitizer, Etanidazole. The resulting classes were compared with each other and with the classes formed from the previous database. RESULTS: The rules derived by RPA from our previous database correctly grouped the tumors in the new database into unique classes of similar outcome. RPA could successfully use either survival or local-regional control of disease as the measure of outcome. As judged by comparison of the 95% confidence intervals, the outcome of the classes in the new database is essentially indistinguishable from the outcome of the classes in the previous database. CONCLUSION: RPA-derived rules provide a reliable method to assort head and neck tumors into unique classes that are predictive of outcome. These rules can be successfully applied to new databases that were not used in the creation of the rules and thereby validate the methodology.
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Carcinoma de Células Escamosas/clasificación , Neoplasias de Cabeza y Cuello/clasificación , Estadificación de Neoplasias/métodos , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Bases de Datos Factuales , Etanidazol/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Matemática , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Misonidazol/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Análisis de Varianza , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Dosificación Radioterapéutica , Insuficiencia del Tratamiento , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. METHODS AND MATERIALS: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66-74 Gy in 33-37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (> or = 14.5 gm% for men, > or = 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model. RESULTS: Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable. CONCLUSION: Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.
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Anemia/complicaciones , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Etanidazol/uso terapéutico , Neoplasias de Cabeza y Cuello/radioterapia , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Análisis de Varianza , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tasa de Supervivencia , Insuficiencia del TratamientoRESUMEN
Survival outcome of 1592 analyzable patients on four Radiation Therapy Oncology Group (RTOG) studies in inoperable non-small cell lung cancer were studied utilizing a recursive partitioning analysis (RPA). This approach creates a regression tree according to prognostic variables which partitions into homogenous subsets according to survival. Four protocols, RTOG 83-11, 83-21, 84-03 and 84-07 were analyzed. 83-11 and 84-07 were studies utilizing irradiation with alterfractionation; 83-21 and 84-03 were studies evaluating thymocin with irradiation and prophylactic cranial irradiation with thoracic irradiation respectively. Nine pretreatment variables and one treatment variable were analyzed. Adjustment for radiotherapy effect was made in the accelerated treatment protocol (84-07). Overall, median survival for the entire group was 9.0 months with 17% alive at 2 years. Univariate analysis suggests that KPS, < or = 70 vs. 80-100, pleural effusion, weight loss, < or = 5% vs. 5%, age, 60+ vs. < 60, T stage (T1 and T2 vs. T3 and T4) and N stage (N- vs. N+) were important prognastic factors. Radiation dose, sex, race and histology were not univariate prognastic factors. RPA identified KPS as the most significant covariate (median survival 5.9 mos. < or = 70 vs. 9.9 mos. 80-100). Within KPS 80-100 other splits occurred for N stage, age, weight loss and radiation therapy dose. KPS < or = 70 split at pleural effusion only. The best overall RPA tree has four distinct classes with median survival times ranging from 3.3 to 12.6 months. The RPA classes were validated in an independent non-small cell lung cancer dataset. This analysis may allow more intelligent stratification and study-design for future RTOG trials in inoperable non-small cell lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Anciano , Análisis de Varianza , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Método Doble Ciego , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Tasa de SupervivenciaRESUMEN
PURPOSE: RTOG Protocol 90-20 was designed to evaluate the effect of the hypoxic cell sensitizer Etanidazole (SR-2508) on locally advanced adenocarcinoma of the prostate treated with concurrent external beam irradiation. METHODS AND MATERIALS: Patients with biopsy-proven adenocarcinoma of the prostate with locally advanced T2b, T3, and T4 tumors were eligible for this study. No patients with disease beyond the pelvis were eligible. Serum prostate specific antigen (PSA) was mandatory. All patients received definitive external beam irradiation using standard four-field whole pelvis treatment to 45-50 Gy, followed by a cone down with a minimum total dose to the prostate of 66 Gy at 1.8-2.0 Gy/fraction over 6.5-7.5 weeks. Etanidazole was delivered 1.8 g/m2 given 3 times a week to a total of 34.2 g/m2 or 19 doses. RESULTS: Thirty-nine patients were entered onto the study. Three patients refused treatment; therefore, 36 patients were eligible for further evaluation. Median follow-up was 36.9 months from treatment end. All patients had elevated initial PSA levels, and 18 patients had PSAs of > 20 ng/ml. Tumor classification was T2, 12 patients (33.3%); T3, 22 patients (61.1%); and T4, 2 patients (5.6%). Complete clinical response, defined as PSA < 4 ng/ml and complete clinical disappearance, was attained in 17.9% of (5/28 pts) with information at 90 days and 56% of patients by 12 months following treatment. Relapse-free survival was 13% at 3 years with PSA < 4 ng/ml. There were no Grade 4 or 5 toxicities, either acute (during treatment) or in follow-up. CONCLUSIONS: Results of this trial regarding PSA response and clinical disappearance of disease are similar to historical controls and do not warrant further investigation of etanidazole as was done in this trial. Drug toxicity that, in the past, has been unacceptably high with other hypoxic cell sensitizers does not appear to be a significant problem with this drug.
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Adenocarcinoma/radioterapia , Etanidazol/uso terapéutico , Neoplasias de la Próstata/radioterapia , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Adenocarcinoma/sangre , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Radioterapia/efectos adversosRESUMEN
During the past 25 years, the Radiation Therapy Oncology Group (RTOG) has played a major role in head and neck cancer clinical research. The major research themes for recent and currently active trials have been: (a) combined modality therapy, (b) altered fractionation radiotherapy, (c) hypoxic cell sensitizers, (d) organ preservation, (e) chemoprevention, and (f) clinical/laboratory correlations. For advanced operable disease, the RTOG showed improved local-regional control with postoperative radiotherapy as compared to preoperative radiotherapy for carcinoma of the supraglottic larynx and hypopharynx. This established the use of surgery followed by postoperative radiotherapy as the standard treatment in subsequent RTOG and Intergroup trials for operable disease. For advanced inoperable disease, the RTOG demonstrated the feasibility of testing altered fractionation radiotherapy in a multiinstitutional clinical trials setting. A Phase III trial comparing hyperfractionation and accelerated fractionation to conventional fractionation is now in progress. Phase I/II combined modality studies established the efficacy of concurrent high-dose cisplatin and radiotherapy in the treatment of advanced disease and provided the basis for further testing in Phase III trials for nasopharyngeal carcinoma, larynx preservation, and high-risk advanced operable disease. Analysis of the extensive RTOG Head and Neck Cancer database established the incidence of second malignancies and their adverse impact on patients whose initial tumors were cured by radiotherapy, and provided the basis for chemoprevention trials. Recursive partitioning analysis identified 6 distinct prognostically homogeneous patient groups based on pretreatment tumor or patient characteristics and/or treatment variables. Retrospective analysis identified tumor p105 antigen density as an independent prognostic indicator in patients irradiated for head and neck cancer. Future trials will continue to focus on the reduction of morbidity and mortality, and improvement of the quality of life of head and neck cancer patients through innovative radiotherapy delivery, multimodality approaches, use of chemical and biological modifiers, and other novel therapies, identification of clinical and biological prognostic indicators, and prevention or diminution of acute morbidity and late complications of the disease and its treatment.
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Ensayos Clínicos como Asunto , Neoplasias de Cabeza y Cuello/radioterapia , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/prevención & control , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Predicción , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/prevención & control , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Estadificación de Neoplasias , Calidad de Vida , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: The Radiation Therapy Oncology Group conducts large-scale prospective, randomized trials to test new concepts in cancer patient care and provide information about pretreatment and treatment factors that may influence outcome. METHODS: Recursive partitioning analysis (RPA) was used to examine the data derived from 2105 patients. RPA grouped patients according to the influence of tumor, of host, and of treatment variables on outcome. RESULTS: For survival, the most important factor was T classification. For lesions less than T3, the primary tumor was the next most important factor, whereas for T3 and T4 lesions the Karnofsky score was the next most predictive factor. Six distinct groups were formed by RPA, with median survivals ranging from 6.8 to 151.8 months. For local-regional control, the N classification was the most important factor. For patients with no adenopathy, T classification was the next most important factor, whereas for patients with adenopathy, the number of treatment fractions was the next most important factor. Such analysis created 5 distinct groups. In the most favorable, the median time to local-regional relapse has not yet been reached. In the least favorable group, fewer than 50% of the patients experienced complete response at any time following treatment. CONCLUSIONS: RPA clarifies the relative importance and potential interactions of pretreatment and treatment variables and should permit more accurate stratification of patients in future trials.
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Carcinoma de Células Escamosas/radioterapia , Interpretación Estadística de Datos , Neoplasias de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Predicción , Neoplasias de Cabeza y Cuello/patología , Humanos , Estado de Ejecución de Karnofsky , Metástasis Linfática , Masculino , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Prospectivos , Dosificación Radioterapéutica , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Conventional radiotherapy for treatment of carcinoma of the cervix consists of five daily fractions of 1.80-2.00 Gy, 5 days/week, up to 40.00-50.00 Gy, followed by intracavitary brachytherapy to complete a paracentral dose ranging from 70 to 90 Gy and a lateral pelvic wall dose ranging from 50 to 60 Gy. This results in tumor control in the pelvis for at least 91% of patients with Stage IB disease. However, survival rates at 5-year follow-up have ranged from 49% to 69% for patients with Stage III disease and 25% to 34% for patients with Stage IVA disease. Attempts to improve clinical results for patients with more advanced stages of disease have included hypofractionated and hyperfractionated radiotherapy, accelerated fractionation, and concomitant boost. However, no improvement of tumor control or survival has been obtained. Hyperfractionated external pelvic radiation remains undefined as a method of improving results. Extended-field prophylactic irradiation of the paraaortic lymph nodes has shown significant value in a study group setting. Early diagnosis and prevention continue to be the most promising approaches in the control of carcinoma of the cervix.
Asunto(s)
Neoplasias del Cuello Uterino/radioterapia , Femenino , Humanos , Radioterapia/métodos , Dosificación RadioterapéuticaRESUMEN
OBJECTIVES: To investigate whether irradiation to the standard pelvic field only improves the response rate and survival in comparison with pelvic plus para-aortic irradiation in patients with high-risk cervical carcinoma, and to investigate patterns of failure and treatment-related toxicity. DESIGN: Randomized controlled trial from November 1979 to October 1986, with stratification by histology, para-aortic nodal status, and International Federation of Gynecology and Obstetrics (FIGO) stage. SETTING: Radiation Therapy Oncology Group (RTOG) multicenter clinical trial. PATIENTS: A total of 367 patients with FIGO stage IB or IIA primary cervical cancers measuring 4 cm or greater in lateral diameter or with FIGO stage IIB cervical cancers were randomized to RTOG protocol 79-20 to receive either standard pelvic only irradiation or pelvic plus para-aortic irradiation. INTERVENTION: Pelvic only irradiation consisted of a midplane pelvic dose of 40 to 50 Gy in 4.5 to 6.5 weeks with daily fractions of 1.6 to 1.8 Gy for 5 d/wk. Pelvic plus para-aortic irradiation delivered 44 to 45 Gy in 4.5 to 6.5 weeks with daily fractions of 1.6 to 1.8 Gy for 5 d/wk. A total dose of 4000 to 5000 mg/h of radium equivalent or 30 to 40 Gy was provided by intracavitary brachytherapy to point A. MAIN OUTCOME MEASURES: Response rate, overall and disease-free survival, patterns of failure, and treatment-related toxicities. RESULTS: Ten-year overall survival was 44% for the pelvic only irradiation arm and 55% for the pelvic plus para-aortic irradiation am (P = .02). Cumulative incidence of death due to cervical cancer was estimated as significantly higher in the pelvic only arm at 10 years (P = .01). Disease-free survival was similar in both arms; 40% for the pelvic only arm and 42% for the pelvic plus para-aortic arm. Locoregional failures were similar at 10 years for both arms (pelvic only, 35%; pelvic plus para-aortic, 31%; P = .44). In complete responders, the patterns of locoregional failures were the same for both arms, but there was a lower cumulative incidence for first distant failure in the pelvic plus para-aortic irradiation arm (P = .053). Survival following first failure was significantly higher in the pelvic plus para-aortic arm (P = .007). A higher percentage of local failures were salvaged long-term on the pelvic plus para-aortic arm compared with the pelvic only arm (25% vs 8%). The cumulative incidence of grade 4 and 5 toxicities at 10 years in the pelvic plus para-aortic arm was 8%, compared with 4% in the pelvic only arm (P = .06). The death rate due to radiotherapy complications was higher in the pelvic plus para-aortic arm (four [2%] of 170) compared with the pelvic only arm (one [1%] of 167) (P = .38). The proportion of deaths due to radiotherapy complications in the pelvic plus para-aortic arm was higher than in the pelvic only arm (four [6%] of 67 vs one [1%] of 85; P = .24). If the patient had abdominal surgery prior to para-aortic irradiation, the estimated cumulative incidence of grade 4 and 5 complications was 11%, compared with 2% in the pelvic only arm. CONCLUSIONS: The statistically significant difference in overall survival at 10 years for the pelvic plus para-aortic irradiation arm, without a difference in disease-free survival, can be explained by the following two factors: (1) a lower incidence of distant failure in complete responders and (2) a better salvage in the complete responders who later failed locally.
Asunto(s)
Irradiación Linfática , Neoplasias del Cuello Uterino/radioterapia , Abdomen , Adulto , Anciano , Braquiterapia , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática/prevención & control , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Radioterapia de Alta Energía , Análisis de Supervivencia , Insuficiencia del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: A review of the Patterns of Care Studies Process Survey data on carcinoma of the cervix conducted on patients in 1978, 1983, and 1988-89 was carried out to identify changes or trends in the demographics, evaluation, and treatment that might have occurred over this time period. METHODS AND MATERIALS: Patterns of Care Studies conducted surveys on patients treated by radiation therapy for cervical carcinoma in 1978, 1983, and 1988-89. These surveys have compiled demographic and treatment data on a total of 993 patients. There is outcome data for the 1978 and 1983 surveys, but not for the 1988-89 survey because follow-up has not been collected yet. The demographic and treatment delivery data on all three surveys has been reviewed and analyzed and is the subject of this study. RESULTS: There was no difference in the age distribution at the time of diagnosis of the patients in these surveys. The percentage of black patients remained constant in the three surveys, 19%, 17%, and 21%, respectively. The percentage of white patients was 76%, 78%, and 67%, but that of nonwhite/nonblack patients was 3%, 4%, and 12% (p < 0.001). The distribution of patients by stage was similar in the first two surveys. In the third survey, there was a decrease in the percentage of patients with Stage IA and IB (first = 35%; second = 38%; third = 29%) with a concurrent increase in Stage IIIA and IIIB patients (first = 20%; second = 18%; third = 26%). The surveys showed a major change in the pretreatment evaluation tests used. There was a progressive decrease in the use of intravenous pyelogram (IVP) (86 to 42%), barium enema (58 to 32%), cystoscopy for patients Stage IIB and higher (64 to 52%), and lymphangiography (18 to 14%). The use of abdominal or pelvic computed tomography dramatically increased from 6 to 70% between the first and third surveys. The use of 60Co units decreased from 35 to 2% from the first to the third survey [6 to 0% for short source-surface distance (SSD) 60Co units]. Point dose calculations for the intracavitary therapy increased from 78% in the 1978 survey to 95% in the third survey. As determined by the total dose delivered to the paracentral points, more patients (75.1%) were treated according to the Patterns of Care recommended guidelines in the 1988-89 survey than in the 1983 survey (63.6%). Chemotherapy was given to 12% of the patients undergoing radiation therapy during the period of the third survey, but these data are not available for the first and second surveys. CONCLUSION: Review of the Carcinoma of the Cervix Patterns of Care studies discloses significant changes in the demographics, patient evaluation, and radiation therapy techniques during the period of the studies. The potential impact of these changes on treatment outcome cannot be determined at this time until longterm follow-up for the 1988-89 survey is available, but improvements in the processes of care should lead to improvements in outcome.
Asunto(s)
Radioterapia/métodos , Neoplasias del Cuello Uterino/radioterapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Braquiterapia/métodos , Braquiterapia/normas , Radioisótopos de Cobalto/uso terapéutico , Demografía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Grupos Raciales , Radioterapia/tendencias , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Población BlancaRESUMEN
PURPOSE: The objectives of this study were to determine the efficacy and toxicity of Etanidazole (ETA), a hypoxic cell sensitizer, when combined with conventional radiotherapy (RT) in the management of advanced head and neck carcinomas. METHODS AND MATERIALS: From March 1988 to September 1991, 521 patients who had Stage III or IV head and neck carcinomas were randomized to receive conventional RT alone (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 fractions per week) or RT+ETA (2.0 g/m2 thrice weekly for 17 doses), of whom 504 were eligible and analyzable. Treatment assignments were stratified before randomization according to the primary site (oral cavity + hypopharynx vs. supraglottic larynx + oropharynx + nasopharynx), T-stage (T1-3 vs. T4), and N-stage (N0-2 vs. N3). Pretreatment characteristics were balanced. In the RT-alone arm, 39% of patients had T3 and 34% had T4 disease, whereas in the RT+ETA arm, 42% of patients had T3 and 33% had T4 disease. Thirty-eight percent of the RT-alone patients and 37% of the RT+ETA patients had N3 disease. The median follow-up of surviving patients was 3.38 years, with a range between 0.96 and 5.63 years. RESULTS: One hundred and ninety-four of the 252 (77%) RT+ETA patients received at least 14 doses of the drug. Overall RT protocol compliance rate was 82% in the RT-alone arm and 86% in the RT+ETA arm. No Grade 3 or 4 central nervous system or peripheral neuropathy was observed in the RT+ETA arm. Eighteen percent of the patients developed Grade 1 and 5% developed Grade 2 peripheral neuropathy. Other drug related toxicities included nausea/vomiting (27%), low blood counts (15%), and allergy (9%). Most of these toxicities were Grade 1 and 2. The incidence of severe acute and late radiation effects were similar between the two arms. The 2-year actuarial local-regional control rate (LCR) was 40% for the RT-alone arm and 40% for the RT+ETA arm. Two-year actuarial survival was 41% for the RT-alone arm and 43% for the RT+ETA arm (p = 0.65). Multivariate analyses were performed to investigate the influence of covariates on treatment effects. A strong treatment interaction with N-stage was revealed: LCR (50% vs. 40% at 2 years), RT+ETA improved for patients with N0-2 disease but not for N3 patients (22% for RT+ETA and 40% for RT). Further analyses showed that RT+ETA was more advantageous in N0-1 patients, with a 2-year LCR of 55% for RT+ETA vs. 37% for RT only (p = 0.03). A similar phenomenon was observed when using survival as the end point. CONCLUSION: The results showed that adding Etanidazole to conventional RT produced no global benefit for patients who had advanced head and neck carcinomas. There was a suggested benefit for patients who had N0-1 disease, and that needs to be confirmed by another study.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Etanidazol/uso terapéutico , Neoplasias de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Etanidazol/efectos adversos , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia/efectos adversos , Tasa de Supervivencia , Insuficiencia del TratamientoRESUMEN
PURPOSE: The objective of this study was to examine the incidence of late effects of hyperfractionated radiotherapy for head and neck cancer as a function of the dose delivered, as well as the daily interfraction interval. In addition, we wished to examine the influence of other prognostic factors including age, gender, primary site, T- and N-stage, and overall stage on the late effects of hyperfractionated radiotherapy. METHODS AND MATERIALS: Between 1983 and 1987, 479 patients with advanced head and neck cancer were entered on a Phase ILE/II dose escalation trial of hyperfractionated radiotherapy. They were randomly assigned to receive a dose of 67.2, 72.0, 76.8, or 81.6 Gy, delivered at 1.2 Gy/fraction, twice a day (BID), 5 days/week. Of the 451 analyzable patients, 399 patients who received > or = 64.8 Gy and had a follow-up > 90 days were eligible for this study. Acute and late effects were scored with the RTOG/EORTC late radiation morbidity scoring scheme. For this analysis, patients were subclassified by the actual doses delivered and by an average daily interfraction interval of < or = 4.5 h or > 4.5 h. The incidence of late effects was estimated using a cumulative incidence approach. RESULTS: Fifty-nine patients received 67.2 +/- 2.4 Gy, 119 received 72.0 +/- 2.4 Gy, 98 received 76.8 +/- 2.4 Gy, and 123 received 81.6 +/- 2.4 Gy. The proportion of patients treated with a daily interfraction interval of > 4.5 h was 32, 50, 43, and 71%, respectively. The four treatment groups were well balanced with respect to pretreatment characteristics. The median follow-up was 1.71 years (range: 0.24-9.6) for all evaluable patients and 6.12 years for 85 alive patients. There was no significant difference in the incidence of late effects between the different dose levels. At 5 years, the cumulative incidence of late effects was 17, 14, 20, and 13% for grade 3, and 7, 3, 7, and 5% for grade 4. However, the incidence of late effects differed significantly with respect to daily interfraction interval. The cumulative incidence of grade 4 late effects increased from 6.3% at 2 years to 7.5% at 3 years to 8.0% at 4 years and 8.6% at 5 years with an interval of < or = 4.5 h, while it remained at a constant of 2.0% with an interval of > 4.5 h during the same period (p = 0.0036). Multivariate analysis showed that among the prognostic factors examined, daily interfraction interval of < or = 4.5 h was the only significant independent prognostic factor for the development of grade 3+ or grade 4 late effects (p = 0.0167 and p = 0.0013, respectively). CONCLUSION: Results of this randomized Phase ILE/II trial of hyperfractionated radiotherapy in head and neck cancer showed no apparent dose-response relationship for late effects within the range of 67.2-81.6 Gy. Daily interfraction interval was a significant independent factor for the development of late effects in a multivariate analysis.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Dosificación Radioterapéutica , Adulto , Carcinoma de Células Escamosas/patología , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia/efectos adversos , Factores de TiempoRESUMEN
PURPOSE: RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end points of this study include tumor clearance rate, effect on serum testosterone, loco-regional control, disease-free interval, and survival. METHODS AND MATERIALS: Eligible patients were those with histologically confirmed locally advanced adenocarcinoma, clinical Stage B2 (T2B) and C (T3) without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients were stratified by clinical stage, histological grade, and nodal status, and were randomized to receive either Megestrol 40 mg three times per day by mouth, or Diethylstilbestrol 1 mg three times per day by mouth. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44-46 Gy, 1.8-2 Gy per day to the regional lymphatics, followed by a boost to the prostate consisting of 20-25 Gy, 1.8-2 Gy per day, to a total of 65-70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 198 were analyzable. RESULTS: Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs. 7%) and fluid retention (21% vs. 6%). The incidence of thromboembolic phenomena was comparable (8% vs. 5% in the Megestrol arm). Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level. Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 7 years, 16% of patients on the Megace arm and 21% of patients on the DES arm manifested evidence of local failure. CONCLUSIONS: The results of the study indicate comparable efficacy (using tumor clearance as an end point) of DES and Megestrol. Although DES appears more effective in suppressing testosterone, it is also associated with a higher incidence of drug-related toxicity.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Dietilestilbestrol/uso terapéutico , Megestrol/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/secundario , Terapia Combinada , Dietilestilbestrol/efectos adversos , Humanos , Masculino , Megestrol/efectos adversos , Estadificación de Neoplasias , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Dosificación RadioterapéuticaRESUMEN
Carcinoma of the breast is a disease that is associated with 10-year recurrence rates of 25% in operable patients with no spread to the axillary nodes and 75% in patients in whom the tumor has extended to the axillary nodes. Locoregional recurrence rates of close to 50% have been reported in patients with Stage III disease. Adjuvant prophylactic postoperative irradiation can reduce locoregional recurrences to less than 10%. When locoregional recurrence occurs after mastectomy, therapeutic irradiation is required. It can achieve tumor control in at least 50% of cases. The best conditions exist when a surgical procedure can achieve gross removal of the recurrent tumor before irradiation and when the fields of irradiation encompass the chest wall and pertinent lymph node areas. The required dose of radiation is lower after excision of the tumor, and the chances of local tumor control are higher. The dose of radiation must be 4500-5000 cGy (fractions of 180-200 cGy) to the subclinical disease and a boost of 1000-1500 cGy added to the known tumor areas. Distant metastatic manifestations must be dealt with for palliative purposes, except in the case of isolated supraclavicular metastasis, where radical irradiation can achieve cure. The need exists for a definition of the role of systemic therapy for locoregional recurrence, and for the development of the optimal integration of systemic chemotherapy and local radiotherapy in patients with locoregional or distant breast cancer recurrences.