RESUMEN
BACKGROUND: The optimal treatment of elderly patients with Hodgkin's lymphoma (HL) is still a matter of debate. Since many of these patients receive combined modality treatment, we evaluated the impact of different radiation field sizes, that is extended-field (EF) or involved-field (IF) technique when given after four cycles of chemotherapy. PATIENTS AND METHODS: In the multicenter HD8 study of the German Hodgkin Study Group, 1204 patients with early-stage unfavorable HL were randomized to receive four cycles of chemotherapy followed by either radiotherapy (RT) of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). A total of 1064 patients were assessable for the analysis. Of these, 89 patients (8.4%) were 60 years or older. RESULTS: Elderly patients had a poorer risk profile. Acute toxicity from RT was more pronounced in elderly patients receiving EF-RT compared with IF-RT [World Health Organization (WHO) grade 3/4: 26.5% versus 8.6%)]. Freedom from treatment failure (FFTF, 64% versus 87%) and overall survival (OS, 70% versus 94%) after 5 years was lower in elderly patients compared with younger patients. Importantly, elderly patients had poorer outcome when treated with EF-RT compared with IF-RT in terms of FFTF (58% versus 70%; P = 0.034) and OS (59% versus 81%; P = 0.008). CONCLUSION: Elderly patients with early-stage unfavorable HL generally have a poorer risk profile and outcome when compared with younger patients. Treatment with EF-RT instead of IF-RT after chemotherapy has a negative impact on survival of elderly patients and should be avoided.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Traumatismos por Radiación/etiología , Adolescente , Adulto , Anciano , Bleomicina/uso terapéutico , Terapia Combinada , Ciclofosfamida/uso terapéutico , Dacarbazina/uso terapéutico , Progresión de la Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Alemania , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/uso terapéutico , Procarbazina/uso terapéutico , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Vinblastina/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
Radiosensitizers represent an enticing concept in tumor therapy. As ionizing radiation affects both neoplastic and normal tissues, its effects are generally non-specific. The aim of applying a radiosensitizing agent is to achieve a maximum effect on tumor tissue, while minimizing the damage to normal tissues. A variety of parameters such as the oxygen supply and the state in the cell cycle, need to be taken into account when evaluating a potential radiosensitizer. Most of the previously known radiosensitizers are neither selective nor tumor specific. In this article, we review the properties and radiosensitizing potential of Photofrin II. Photofrin II is well-known as a photosensitizing agent in photodynamic therapy. In recent years, a radiosensitizing potential of the substance has been demonstrated, specifically increasing the sensitivity of solid tumor tissues, especially of radio-resistant, hypoxic tumor cells, to radiation. This radiosensitizing effect has been demonstrated both by in vitro studies and by animal experiments. Several studies with tissue cultures have demonstrated a radiosensitizing effect of Photofrin II in glioblastoma (U-373MG) and bladder cancer cell lines (RT-4). No effect was noted in colon carcinoma cell lines (HT-29). Unpublished data of additional cell lines will be mentioned in the review. Animal experiments with Lewis sarcoma and with bladder cancer have moreover demonstrated an in vivo effect of Photofrin II as a radiosensitizer. The mechanism of this radiosensitizing effect is not completely understood. In vitro data, however, support the hypothesis that the radiosensitizing action involves OH-radicals in addition to a potential impairment of repair mechanisms after sublethal damage of ionizing radiation. Moreover, early results of a phase I trial are available and document the potential feasibility of the application of Phototofrin II as a radiosensitizing agent in clinical practice.
Asunto(s)
Éter de Dihematoporfirina/uso terapéutico , Rayos gamma/uso terapéutico , Neoplasias/radioterapia , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Animales , Ensayos Clínicos como Asunto , HumanosRESUMEN
In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up. By QCA the acute lumen gain measured 2.2+/-0.8 mm, the late lumen loss at 3 months was 0.1+/-0.5 mm and at 6 months 0.4+/-0.7 mm. By IVUS luminal cross-sectional area increased from 1.5+/-1.2 mm(2) to 7.9+/-1.9 mm(2) (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2+/-1.0 mm(2) (p=0.191), but increased to 0.7+/-0.6 mm(2) (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1+/-1.7 mm(2). Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3+/-1.9 mm(2) (p<0.001), and showed a further increase by 0.7+/-2.9 mm(2) at 6 months. Positive remodelling could be demonstrated also at the reference segment. In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.
Asunto(s)
Angioplastia Coronaria con Balón/métodos , Braquiterapia/métodos , Vasos Coronarios/diagnóstico por imagen , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/prevención & control , Recuperación de la Función , Túnica Íntima/diagnóstico por imagen , Terapia Combinada , Vasos Coronarios/crecimiento & desarrollo , Vasos Coronarios/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.
Asunto(s)
Envejecimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Administración Oral , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Enfermedad de Hodgkin/patología , Humanos , Infusiones Intravenosas , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Even today patients who suffer from mantle cell lymphoma have a poor prognosis, especially when the CNS is involved. To confirm the diagnosis of meningeosis lymphomatosa, asservation of the liquor cerebrospinalis is necessary. During this procedure, intrathecal chemotherapy may be given if there is clinical evidence of meningeosis. If lumbar puncture cannot be performed, a lateral suboccipital puncture may be an alternative approach. PATIENTS AND METHODS: We report the case of a 65-year-old patient who suffered from mantle cell lymphoma stage IV. The patient presented with symptoms of progressive paraparesis of both legs and incontinence, with tumor mass intradural from the 12th thoracic vertebra to the level of S1. During irradiation, the patient developed symptoms of diffuse meningiosis lymphomatosa. The conventional lumbar puncture was impossible, because of tumor present in the thoracico-lumbar junction. RESULTS: A suboccipital puncture was performed for both collecting cerebrospinal fluid and application of chemotherapy (cytosine arabinoside/dexamethasone). This lead to remarkable improvement of the patient's clinical symptoms. CONCLUSIONS: The suboccipital cervical puncture was performed without complications. A variation of the intrathecal approach is described, which may serve as alternative when conventional lumbar puncture is not possible.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células del Manto/tratamiento farmacológico , Neoplasias Meníngeas/secundario , Neoplasias de la Médula Espinal/secundario , Anciano , Líquido Cefalorraquídeo/citología , Quimioterapia Adyuvante , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Humanos , Inyecciones Espinales/métodos , Linfoma de Células del Manto/radioterapia , Masculino , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/radioterapia , Cuidados Paliativos , Neoplasias de la Médula Espinal/tratamiento farmacológico , Neoplasias de la Médula Espinal/patologíaRESUMEN
The biological effects of radiation affect both neoplastic and normal tissues. The nature and extent of such effects, however, depend on selected biological parameters (e.g., oxygen supply, cell cycle) and can be modified by chemical agents such as radiosensitizers, radioprotectors and chemotherapeutic agents. A precise control of the mode of action of the radiation is important in order to achieve the maximum effect on tumor tissue, while minimizing the effect on normal tissues. Most of the known and routinely used radiosensitizers are neither selective nor tumor specific. This article reviews a new selective and specific modality that increases the sensitivity of solid tumor tissue, especially of radio resistant, hypoxic tumor cells, to radiation. This modality is currently under early clinical evaluation and encompasses the application of Photofrin II, which is already used as a photosensitizer in photodynamic therapy (PDT) at predetermined times prior to irradiation.
Asunto(s)
Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Porfirinas/farmacocinética , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Humanos , Neoplasias/diagnóstico , Porfirinas/administración & dosificación , Porfirinas/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/farmacocinéticaRESUMEN
BACKGROUND: Vascular brachytherapy (VBT) has been proven to reduce restenosis rate and unwanted cardiac events in several randomized trials. Long-term data on populations at high risk for re-interventions are few. The aim of this study was to assess the acute and one-year outcome of beta-radiation in coronary in-stent restenoses with a high likelihood of recurrence. METHODS: In 79 patients, VBT using 90Yttrium/Strontium or 32Phosphorus, was performed. Clinical and angiographic follow-up was carried out after 6 months and 1 year. RESULTS: 44.4 % of patients had three-vessel coronary artery disease and a high prevalence of cardiovascular risk factors and comorbidity. Mean lesion length was 36.8+/-18.9 mm. VBT was successful in all patients. Fractionation of VBT was necessary in 2,5 %. Acute gain of luminal diameter was 2.15+/-0.89 mm. During the hospital stay one acute myocardial infarction (AMI) not associated with VBT occurred. After 6 months loss of luminal diameter measured 0.39+/-0.47 mm, equaling a restenosis rate (RR) of 16.8 % (1 year: 0.60+/-0.56 mm, RR 33.5 %). 18.9 % of patients required revascularization of the target lesion (1 year: 29.5 %). After 6 months, all patients survived, three had an AMI after discontinuation of clopidogrel, one of them was asymptomatic (1 year: 1 cardiac death, 2 symptomatic AMI). CONCLUSION: Beta-VBT in patients at a high risk for recurrence after angioplasty is feasible and safe. Though the clinical and angiographic results at 1 year showed some impairment as opposed to the 6-months-follow-up, they nevertheless are largely superior to those patients from historic controls not treated with VBT.
Asunto(s)
Braquiterapia/métodos , Reestenosis Coronaria/radioterapia , Anciano , Comorbilidad , Angiografía Coronaria , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/epidemiología , Estenosis Coronaria/etiología , Estenosis Coronaria/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Prevalencia , Factores de Riesgo , Prevención Secundaria , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: The prognosis for patients with malignant astrocytoma or brain metastases is often fatal despite intensive therapy. Therefore we wished to elucidate whether the quality of life (QoL) is a determinant of overall survival (OAS). PATIENTS AND METHODS: From 1997 to 2000 153 patients with brain tumours were screened; 39 patients (26%) refused to participate and further 47 patients were excluded (cerebral impairment 14%, amaurosis/ language problems 3%, Karnofsky performance score < 50% 7%, death 8%, non-compliance 7%). Thus, 57 patients were analysed (33 with primary brain tumours, 24 with brain metastases). With the FACT-G questionnaire cancer-specific aspects of health-related QoL were assessed. RESULTS: Patients with metastases showed a lower QoL in the physical sphere than patients with astrocytoma, but there were no significant differences in OAS. Median survival of patients with good QoL was 31.3 months versus 14.2 months in patients with bad QoL. Only the two variables 'living with a spouse' and FACT-G sum score had a statistically significant influence on survival (p = 0.033 and p = 0.003) modelled by the Cox-PH regression. Patients who did not live with a spouse had shorter survival times than the other patients. CONCLUSION: Health-related QoL can serve to identify a patient group with higher risks of death.
Asunto(s)
Astrocitoma/radioterapia , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Glioblastoma/radioterapia , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Astrocitoma/mortalidad , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Femenino , Estudios de Seguimiento , Glioblastoma/mortalidad , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Radioterapia Adyuvante , Análisis de Regresión , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
AIM: We wanted to understand coping strategies specific to different phases up to two years after radiotherapy, to identify patients who are at higher risk of mood disturbances and to characterise the association between coping strategies and psychosocial adaptation. PATIENTS AND METHODS: From 1997 to 2001, 2,169 patients with different diagnoses were screened (27.8% refused to participate). Data of 276 patients from the beginning of radiotherapy (ti1) and 5 follow-up investigations (ti6/2 years) could be analysed. With the FKV (Freiburg Questionnaire Coping with Disease) cancer-specific coping aspects were assessed. The association between coping styles and psychosocial adaptation was evaluated using the Questionnaire on Stress in Cancer Patients (QSC) and the questionnaire on Functional Assessment of Cancer Treatment (FACT-G). RESULTS: 'Active problem-orientated' coping and 'distractions' are the most important coping strategies. Only 'active problem-orientated' and 'depressive' coping showed a significant decrease. We observed higher means on the scales of the FKV in women. Marital status (single, married, divorced/widowed) had a significant influence on active problem-orientated coping and spirituality. Age, children, education, T/M status and curative/ palliative intention of treatment had no influence on coping styles. Breast cancer patients and lymphoma patients demonstrated the highest use of coping strategies after radiotherapy with a significant decrease of 'active problem-orientated coping'. Depressive coping and minimizing importance at ti1 were associated with high psychosocial distress and low quality of life (QoL) at ti6. CONCLUSION: The correlation of coping mechanisms at the beginning of radiotherapy with low QoL and high psychosocial stress at 2 years could help to identify patients at risk for low psychosocial adaptation. Psycho-oncologically trained teams of physicians would best correspond to this profile of needs and would contribute significantly to an ameliorated adaptation of patients to cancer which could lead to higher life satisfaction.
Asunto(s)
Adaptación Psicológica , Neoplasias/psicología , Neoplasias/radioterapia , Radioterapia/psicología , Rol del Enfermo , Trastornos de Adaptación/diagnóstico , Trastornos de Adaptación/psicología , Adulto , Anciano , Neoplasias de la Mama/psicología , Neoplasias de la Mama/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Linfoma/psicología , Linfoma/radioterapia , Masculino , Persona de Mediana Edad , Cuidados Paliativos/psicología , Inventario de Personalidad , Solución de Problemas , Pronóstico , Calidad de Vida/psicología , Ajuste Social , Apoyo Social , Factores Socioeconómicos , EspiritualidadRESUMEN
Restenosis is the limiting entity after percutaneous coronary angioplasty. Vascular brachytherapy for the treatment of in-stent restenosis has been shown to reduce the repeat restenosis rate and the incidence of major adverse events in several randomized trials. Besides the beneficial effects, brachytherapy yielded some unwanted side effects. The development of new stenoses at the edges of the target lesion treated with radiation is termed edge effect. It occurs after afterloading brachytherapy as well as after implantation of radioactive stents. It is characterized by extensive intimal hyperplasia and negative remodeling. As contributing factors the axial dose fall-off, inherent to all radioactive sources, and the application of vessel wall trauma by angioplasty have been identified. The combination of both factors, by insufficient overlap of the radiation length over the injured vessel segment, has been referred to as geographic miss. It has been shown to be associated with a very high incidence of the edge effect. Avoidance of geographic miss is strongly recommended in vascular brachytherapy procedures. Late thrombosis after vascular brachytherapy is of multifactorial origin. It comprises platelet recruitment, fibrin deposition, disturbed vasomotion, non-healing dissection and stent malapposition predisposing to turbulent blood flow. The strongest predictors for late thrombosis are premature discontinuation of antiplatelet therapy and implantation of new stents during the brachytherapy procedure. With a consequent and prolonged antiplatelet therapy, the incidence of late thrombosis has been reduced to placebo levels. Edge effect and late thrombosis represent unwanted side effects of vascular brachytherapy. By means of a thorough treatment planning and prolonged antiplatelet therapy their incidences can be largely reduced. With regard to the very favorable net effect, they do not constitute relevant limitations of vascular brachytherapy.
Asunto(s)
Angioplastia Coronaria con Balón , Braquiterapia/efectos adversos , Reestenosis Coronaria/radioterapia , Trombosis Coronaria/etiología , Stents , Trombosis Coronaria/fisiopatología , Trombosis Coronaria/prevención & control , Esquema de Medicación , Humanos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Retratamiento , Factores de RiesgoRESUMEN
BACKGROUND: The standard therapy for patients with clinically resectable rectal cancer is generally considered to be surgery. If the patient is diagnosed with advanced disease, postoperative radio-chemotherapy (RCT) is usually recommended. In our study we aimed to investigate and analyze the effectiveness and toxicity of preoperative pelvic radiotherapy in combination with 5-fluorouracil (5-FU) in locally advanced rectal cancer. PATIENTS AND METHODS: From June 1999 to September 2001 we evaluated 50 consecutive patients [37 male and 13 female; average age 65.1 (range 46-79.5) years] with locally advanced rectal carcinoma. 32 patients were staged as uT3, 14 as uT4, and 4 as uT2. Regarding N-staging, 22 patients were diagnosed as uN0. 2 patients had distant metastases, with liver metastases in both instances. Conformal irradiation was performed with a box technique (4-field technique) with a dose of 45 Gy (5 x 1.8 Gy per week for a total of 25 sessions). From days 1-5 and 29-33, all patients received 5-FU (500 mg/m(2 ) per day, as a continuous i.v. injection). RESULTS: Remission was observed in 28 patients (56%), with down-staging of at least one T-stage. A better success rate was achieved for patients with deep-seated tumors (64% of the patients in this group). Complete remission was observed in 4 patients (8.0%) and progression in 3 (6.0%). 15 patients had no detectable change in tumor staging (30.0%). A surgical R0 resection could be achieved in 43 patients, an R1 resection (minimal margin) in 7. Side effects and toxicity (common toxicity criteria) of RCT included grade I-II dysuria in 5 patients (10%), grade I-II diarrhea in 20 patients (40%), and severe diarrhea in 2 patients (4.0%). Grade I-II skin reaction was noticed in 22 patients (44.0%), severe skin reaction only in 1 patient. Regarding acute postoperative morbidity, abscess and fistula formation was noted in 8 patients (16.0%), with anastomosis leakage in 7 (14%). CONCLUSION: Preoperative radiotherapy appears to be a feasible therapeutic approach with moderate toxicity and the potential to induce down-staging. The data presented in this study confirm the preliminary reports on this neoadjuvant treatment.
Asunto(s)
Fluorouracilo/administración & dosificación , Terapia Neoadyuvante , Radioterapia Conformacional , Neoplasias del Recto/radioterapia , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: So far, surgery represents the only prospect for cure in patients with pancreatic cancer. Most patients, however, present with locally advanced pancreatic cancer at primary diagnosis. Recently, novel therapeutic regimens with preoperative radiochemotherapy have been developed that may improve long-term survival and resectability rates of patients with locally advanced pancreatic cancer. METHODS: This feasibility study evaluates the preliminary results of neoadjuvant therapy with gemcitabine and 5-fluorouracil (5-FU) or cisplatin. Twenty-six patients suffering from locally advanced pancreatic cancer were considered for preoperative radiochemotherapy. They received radiation (45 Gy) and chemotherapy with simultaneous or sequential gemcitabine and 5-FU (n = 15) or gemcitabine and cisplatin (n = 11) administration prior to surgical resection. RESULTS: Mean patient age was 62.4 +/- 2.6 years and 62% (n = 16) were male. The response rate was 69%, and 11 patients underwent curative surgical resection of the pancreatic cancer. Nine Whipple procedures and two complete pancreatectomies were carried out. In five patients a total of eight surgical complications were observed. Median overall survival was 9.8 months after primary cancer diagnosis (mean 12.0 +/- 1.2). During follow-up no local recurrent disease was detected. CONCLUSIONS: Our findings lead us to conclude that preoperative chemoradiation with 45 Gy, gemcitabine and 5-FU or cisplatin is a powerful therapeutic tool in patients with locally advanced non-resectable pancreatic cancer. Major resections, including vascular reconstructions, are nonetheless associated with increased mortality. Preoperative chemoradiation contributes to improved survival in patients with primary non-resectable pancreatic cancer.
Asunto(s)
Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas/terapia , Anciano , Terapia Combinada , Estudios de Factibilidad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Tasa de SupervivenciaRESUMEN
The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.
Asunto(s)
Antineoplásicos/uso terapéutico , Éter de Dihematoporfirina/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Antineoplásicos/farmacocinética , Éter de Dihematoporfirina/farmacocinética , Femenino , Humanos , Ratones , Ratones Desnudos , Porfirinas/uso terapéutico , Dosificación Radioterapéutica , Distribución Tisular , Trasplante Heterólogo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: The effect of ionizing radiation on tumour tissues can be optimised by adding radiosensitising agents to enhance tumour inactivation. Photofrin II has been approved as a photosensitising agent for the photodynamic therapy (PDT) of selected solid tumours. At present, no chemical modifier has been found to act as a selective radiosensitiser. We report here the first use of Photofrin II as a radiosensitising agent to enhance radiation therapy. PATIENTS: Two patients, one female with unresectable bladder cancer and one male with recurrent inoperable bladder cancer, were treated with radiation therapy (44.8 Gy + 14 Gy boost) of the pelvic region. 24 hours before initiation of therapy the patients were intravenously injected with 1 mg kg(-1) Photofrin II (Axcan, Canada). RESULTS: Magnetic resonance imaging of the pelvis with a standardized protocol demonstrated a reduction in tumour volume of approximately 40% in the female patient and 35% in the male patient. The female patient was operated upon after conclusion of radiotherapy, the male patient refused the operation. No severe side effects were observed. CONCLUSION: Photofrin II is a promising radiosensitising agent in the treatment of patients with advanced solid tumours.
Asunto(s)
Éter de Dihematoporfirina/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/radioterapia , Anciano , Terapia Combinada , Éter de Dihematoporfirina/sangre , Éter de Dihematoporfirina/farmacocinética , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND AND OBJECTIVE: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. MATERIALS AND METHODS: Several series of animal experiments were performed. The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. RESULTS: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. CONCLUSION: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation.
Asunto(s)
Éter de Dihematoporfirina/farmacología , Fotorradiación con Hematoporfirina , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , División Celular/efectos de los fármacos , Femenino , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: Radiotherapy brings a tumor patient into a special life situation in which different variables play a role of often unknown importance. The goal of this study was to investigate disease specific stress of tumor patients at the beginning of radiotherapy with established psychodiagnostic questionnaires and to evaluate the effect on psychosocial support requirement in order to reduce stress and to improve quality of life and compliance during radiotherapeutical treatment. PATIENTS AND METHODS: 732 patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion (refusals 21.0%, low karnorsky performance status 6.6%, management problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%). Disease specific aspects of stress in the questionnaire (Fragebogen zur Belastung von Krebspatienten, FBK), life situation (LS) and self-defined care requirements (BB) (Figure 1) were self-rated by patients with different tumor types before radiotherapy. Medical and sociodemographic data were also documented. We investigated 446 patients (262 male, 184 female; median age 60.0 years) with different diagnoses (Table 1). RESULTS: Stress was observed mainly due to reduction of efficiency, anxiety and pain on the subscales (Figure 2). Women had a significant higher stress on subscales of pain (p = 0.016) and anxiety (p = 0.009) (Table 2), patients younger than 45 years in the subscale information (p = 0.002) and patients older than 45 and younger than 60 years in the subscale anxiety (p = 0.002) and the total score (p = 0.003) (Table 3). Patients with mamma carcinoma had the highest the stress (Table 4). The maximum percentages of patients under high stress were found for the subscales of efficiency (43%) and anxiety (40%). The support requirement was characterized by the need of more medical information and dialogue with the doctor. We saw a significant correlation of high stress and high care requirement (Tables 5 and 6). CONCLUSIONS: Psychosocial support should be founded on psychosocial stress diagnostic and self-defined care requirement.
Asunto(s)
Neoplasias/psicología , Neoplasias/radioterapia , Apoyo Social , Estrés Psicológico/etiología , Adulto , Femenino , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores Sexuales , Encuestas y CuestionariosRESUMEN
Differentiated thyroid cancer comprises papillary, mixed papillary-follicular and follicular adenocarcinomas. They are mostly hormone-sensitive and respond to thyroid-stimulating hormone (TSH) suppression. The standard treatment is total thyroidectomy, (131)I therapy and thyroid hormone suppression therapy. Adjuvant external radiotherapy is discussed controversially. Most authors recommend adjuvant external radiotherapy for extra-capsular tumor extension. Decision on an individual basis should be made for patients with lymph node involvement. In the case of incomplete surgical resection, external radiotherapy should be applied if second surgery is not possible. For medullary thyroid cancer, external beam radiotherapy seems to be beneficial for patients with surgically inaccessible disease, with microscopic residual or gross tumor after surgery, with recurrent locoregional disease, or with surgically unmanageable metastases. Patients suffering from anaplastic thyroid cancer should receive combined treatment consisting of extensive surgery, external irradiation with total doses up to 60 Gy, and chemotherapy. The combined treatment modality leads to higher local control rates and prolongs survival.
Asunto(s)
Neoplasias de la Tiroides/radioterapia , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirugía , Adenocarcinoma Papilar/patología , Adenocarcinoma Papilar/radioterapia , Adenocarcinoma Papilar/cirugía , Carcinoma/patología , Carcinoma/radioterapia , Carcinoma/cirugía , Carcinoma Medular/patología , Carcinoma Medular/radioterapia , Carcinoma Medular/cirugía , Terapia Combinada , Humanos , Estadificación de Neoplasias , Radioterapia Adyuvante , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del TratamientoRESUMEN
BACKGROUND: Porphyrin metabolism disorders, known as porphyria, represent inherited or acquired diseases. The development of porphyria due to light sensibility occurs especially with exposure to wavelengths in the range of 300-700 nm. Skin reactions and neurovisceral dysfunctions are known side effects of ionizing irradiation. It can be postulated that during or after ionizing irradiation treatment of patients affected with tumor and porphyria, severe side effects might appear, in contrast to patients without porphyria. This paper describes the treatment of 2 patients affected with tumor and concomitant porphyria. PATIENTS: One female patient suffering from intermittent porphyria and breast cancer and one male patient suffering from porphyria cutanea tarda and bladder cancer were treated with ionizing irradiation (electrons and photons). No abnormalities nor any severe general or local side effects could be observed. CONCLUSION: Radiation therapy is not a 'stimulating' factor in activating porphyria symptoms.
Asunto(s)
Neoplasias de la Mama/complicaciones , Porfiria Cutánea Tardía/complicaciones , Porfiria Intermitente Aguda/complicaciones , Neoplasias de la Vejiga Urinaria/complicaciones , Anciano , Neoplasias de la Mama/radioterapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Porfiria Cutánea Tardía/radioterapia , Porfiria Intermitente Aguda/radioterapia , Radioterapia Adyuvante , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/radioterapiaRESUMEN
PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.