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1.
Science ; 184(4144): 1367-9, 1974 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-17810464

RESUMO

Coal palynology and studies of petrified peat indicate major changes in coal-swamp floras and the botanical constituents of coal throughout Pennsylvanian time. The changes are the result of broad climatic shifts and local environmental factors. The most striking is the change from a lycopod-dominated flora to one in which tree ferns were the major element. This change occurred at the Desmoinesian-Missourian (Westphalian-Stephanian) boundary and is probably multicontinental in scope.

2.
Med Phys ; 36(3): 719-24, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19378732

RESUMO

A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.


Assuntos
Neoplasias da Coroide/cirurgia , Monitorização Fisiológica/instrumentação , Neoplasias Orbitárias/cirurgia , Radiocirurgia/métodos , Fenômenos Biofísicos , Neoplasias da Coroide/diagnóstico por imagem , Neoplasias da Coroide/patologia , Movimentos Oculares , Histiocitoma Fibroso Maligno/diagnóstico por imagem , Histiocitoma Fibroso Maligno/patologia , Histiocitoma Fibroso Maligno/cirurgia , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Radiocirurgia/instrumentação , Tomografia Computadorizada por Raios X
3.
Phys Med Biol ; 52(19): 5957-71, 2007 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-17881812

RESUMO

Peripheral radiation can have deleterious effects on normal tissues throughout the body, including secondary cancer induction and cataractogenesis. The aim of this study is to evaluate the peripheral dose received by various regions of the body after ocular treatment delivered with the Model C Gamma Knife, proton radiotherapy with a dedicated ocular beam employing no passive-scattering system, or a CyberKnife unit before and after supplemental shielding was introduced. TLDs were used for stray gamma and x-ray dosimetry, whereas CR-39 dosimeters were used to measure neutron contamination in the proton experiments. Doses to the contralateral eye, neck, thorax and abdomen were measured on our anthropomorphic phantom for a 56 Gy treatment to a 588 mm(3) posterior ocular lesion. Gamma Knife (without collimator blocking) delivered the highest dose in the contralateral eye, with 402-2380 mSv, as compared with 118-234 mSv for CyberKnife pre-shielding, 46-255 mSv for CyberKnife post-shielding and 9-12 mSv for proton radiotherapy. Gamma Knife and post-shielding CyberKnife delivered comparable doses proximal to the treatment site, with 190 versus 196 mSv at the thyroid, whereas protons doses at these locations were less than 10 mSv. Gamma Knife doses decreased dramatically with distance from the treatment site, delivering only 13 mSv at the lower pelvis, comparable to the proton result of 4 to 7 mSv in this region. In contrast, CyberKnife delivered between 117 and 132 mSv to the lower pelvis. In conclusion, for ocular melanoma treatments, a proton beam employing no double scattering system delivers the lowest peripheral doses proximally to the contralateral eye and thyroid when compared to radiosurgery with the Model C Gamma Knife or CyberKnife. At distal locations in the pelvis, peripheral doses delivered with proton and Gamma Knife are of an order of magnitude smaller than those delivered with CyberKnife.


Assuntos
Modelos Biológicos , Terapia com Prótons , Proteção Radiológica/métodos , Radiometria/métodos , Radiocirurgia/métodos , Radioterapia Conformacional/métodos , Neoplasias Uveais/radioterapia , Carga Corporal (Radioterapia) , Simulação por Computador , Humanos , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Eficiência Biológica Relativa , Medição de Risco/métodos , Fatores de Risco
4.
Cancer Res ; 39(6 Pt 2): 2300-3, 1979 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-445427

RESUMO

Major problems in clinical hyperthermia include (a) inhomogeneity of heat distribution in designated tumor volumes due to tissue characteristics and differential blood flow, (b) limitations of heat delivery and control systems for adequate depth penetration and adjustments of temperatures, and (c) the lack of capability of accurate temperature measurements, especially in the area of noninvasive techniques for deep-seated tumors. Examples were given to illustrate the clinical requirements of hyperthermia of superficial, intermediate, and deep-seated tumors.


Assuntos
Temperatura Alta/uso terapêutico , Neoplasias/terapia , Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Neoplasias do Colo/terapia , Feminino , Temperatura Alta/efeitos adversos , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/terapia , Neoplasias Pancreáticas/terapia , Neoplasias Cutâneas/terapia
5.
Cancer Res ; 43(10): 5022-5, 1983 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6883348

RESUMO

Misonidazole (MISO), a hypoxic cell radiosensitizer, has been shown in vivo to enhance tumor cell killing by melphalan (LPAM) with little or no enhancement of normal tissue injury. A Phase I trial was conducted using MISO p.o. 2 hr before i.v. LPAM. The highest doses used were the single maximum tolerated doses of MISO, 4 g/sq m, and LPAM, 0.6 mg/kg. Thirty-five patients were entered; 30 were evaluable for assessment of hematological toxicity, which was predicted to be the dose-limiting toxicity. The median age was 60 years (range, 28 to 72 years). Mild to moderate nausea and vomiting occurred in 80% of patients. Five developed serious hematological toxicity defined as nadir white blood cell count less than 1000/cu mm, platelets less than 20,000/cu mm or 4-week posttreatment white blood cell count less than 2000/cu mm, platelets less than 50,000/cu mm. Four of the toxicities occurred at the LPAM dose of 0.6 mg/kg but were independent of MISO dose. One patient died of infection. Two patients whose tumor demonstrated an objective response to therapy and 10 others with disease stabilization received additional courses. Four patients developed mild MISO neuropathy. Pharmacokinetic studies demonstrated that MISO did not appear to affect the pharmacokinetics of LPAM in plasma. Both LPAM and MISO can be given safely at their individual maximum tolerated dose. This combination will proceed to Phase II trials.


Assuntos
Melfalan/uso terapêutico , Misonidazol/uso terapêutico , Neoplasias/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Adulto , Idoso , Esquema de Medicação , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Misonidazol/efeitos adversos
6.
Cancer Res ; 54(8): 2186-91, 1994 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-8174126

RESUMO

We have shown that sterically stabilized (Stealth) liposomes (SL), can accumulate in the extracellular space within tumors, and may improve pharmacokinetics and therapeutic efficacy of encapsulated doxorubicin (SL-DOX). When SL-DOX were incubated in vitro at different temperatures with 50% bovine serum, approximately 20% of the encapsulated DOX was released at 42 degrees C within 1 min, compared with less than 1% DOX released at 37 degrees C. In vivo, mice were implanted s.c. with C-26 colon carcinoma in both flanks to produce matched tumors 6-10 mm in diameter. Topical hyperthermia treatment consisting of 42 degrees C minimum tumor temperature for 30 min was applied with a microwave device to the tumor on one side only at 1 h after i.v. injection of SL-DOX or free DOX. Tumor DOX concentration in the group which was given injections of SL-DOX and sacrificed 2 h after drug injection was 1.5-fold higher compared with the nonheated tumor in mice given injections of SL-DOX. At 24 h after injection the thermal enhancement ratio for DOX accumulation in tumor remained at 1.5. In addition, there was a 15-fold higher concentration of DOX in tumor from the group given injections of SL-DOX compared to mice given injections of free doxorubicin. To assess therapeutic efficacy, we treated mice with hyperthermia for 15 min either at 1, or at 24 h or at both time points after injection of SL-DOX. We have found that the life span of the group of mice treated with SL-DOX and two 15-min hyperthermia treatments increased 51% compared with control groups receiving the same dosage of SL-DOX but without hyperthermia, and 59% compared to those receiving two hyperthermia treatments but with free DOX. A single hyperthermia treatment either at 1 or 24 h was less effective in increasing life span compared with two treatments, but all groups treated with SL-DOX and single hyperthermia were still superior to the control groups, showing a 27-38% increase in life span.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/terapia , Doxorrubicina/toxicidade , Hipertermia Induzida , Animais , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Terapia Combinada , Relação Dose-Resposta a Droga , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Feminino , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Tempo
7.
Biochim Biophys Acta ; 429(2): 624-8, 1976 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-1260041

RESUMO

A simple method has been developed for the rapid isolation of crystalline glucosephosphate isomerase (EC 5.3.1.9) from rabbit muscle. The enzyme is first bound to cellulose phosphate by adding the ion exchanger to a solution of the crude tissue extract. After filtering and washing the cellulose with buffer, the isomerase is specifically eluted in a batch process by its substrate, glucose 6-phosphate. The entire procedure is very rapid and results in a good recovery (at least 50%) of the enzyme with specific activity of approximately 900 units per mg. The enzyme is homogeneous by polyacrylamide gel electrophoresis in the presence of absence of sodium dodecyl sulfate and by analytical ultracentrifugation.


Assuntos
Glucose-6-Fosfato Isomerase/isolamento & purificação , Músculos/enzimologia , Animais , Cristalização , Glucose-6-Fosfato Isomerase/metabolismo , Peso Molecular , Coelhos
8.
J Clin Oncol ; 13(10): 2606-12, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7595714

RESUMO

PURPOSE: To identify factors associated with radiation pneumonitis (RP) resulting from combined modality therapy (CMT) for lung cancer. MATERIALS AND METHODS: Series published before 1994 that used CMT for the treatment of lung cancer and explicitly reported the incidence of RP are the basis for this analysis. Factors evaluated included the radiation dose per fraction (Fx), total radiation dose, fractionation scheme (split v continuous), type of chemotherapy and intended dose-intensity, overall treatment time, histology (small-cell lung cancer [SCLC] v non-small-cell lung cancer [NSCLC]), and treatment schedule (concurrent v induction, sequential, or alternating CMT). RESULTS: Twenty-four series, including 27 treatment groups and 1,911 assessable patients, met our criteria for inclusion in this analysis. The median total dose of radiation used in the trials analyzed was 50 Gy (range, 25 to 63 Gy). The median daily Fx used was 2.0 Gy (range, 1.5 to 4.0 Gy). Nineteen series included 22 treatment groups and 1,745 patients treated with single daily fractions. Among these patients, 136 received a daily Fx greater than 2.67 Gy. Five series used twice-daily radiotherapy and included 166 patients (Fx, 1.5 to 1.7 Gy). The incidence of RP was 7.8%. In a multivariate analysis, only daily Fx, number of daily fractions, and total dose were associated with the risk of RP (P < .0001, P < .018, and P < .003, respectively). CONCLUSION: In this analysis, the use of Fx greater than 2.67 Gy was the most significant factor associated with an increased risk of RP. High total dose also appears to be associated with an increased risk, but twice-daily irradiation seems to reduce the risk expected if the same total daily dose is given as a single fraction. High-Fx radiotherapy should be avoided in patients who receive CMT with curative intent.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Distribuição de Qui-Quadrado , Terapia Combinada/efeitos adversos , Relação Dose-Resposta à Radiação , Humanos , Incidência , Modelos Logísticos , Neoplasias Pulmonares/tratamento farmacológico , Análise Multivariada , Prognóstico , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/prevenção & controle , Fatores de Risco
9.
J Clin Oncol ; 5(9): 1410-8, 1987 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2442323

RESUMO

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Neoplasias de Cabeça e Pescoço/radioterapia , Metotrexato/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
10.
J Clin Oncol ; 11(5): 857-62, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8487050

RESUMO

PURPOSE: The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible. PATIENTS AND METHODS: From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm. RESULTS: Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047). CONCLUSION: SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.


Assuntos
Carmustina/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Radiocirurgia , Terapia Combinada , Contraindicações , Feminino , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica
11.
Int J Radiat Oncol Biol Phys ; 10(9): 1791-4, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6480462

RESUMO

It is clear that the investigators involved in chemical modification have reached an historical turning point in radiobiology. Studies in the 1960s concentrated on physical and chemical radiobiology, studying dose response relationships and initial chemical reactions. More recently, the area of biochemical radiobiology has been entered and studies of cellular modification of the initial events and cellular repair mechanisms have been initiated. The future would appear to belong to biochemical modulation. The ability to increase or decrease the various cellular components through enzyme blocking or stimulation gives much greater power to our abilities to chemically modify radiation and cytotoxic agents in the future. We are thus come from the winding country lane of sensitizer development to the complex city expressway of chemical modification. Non-nitro-compounds and pyrimidine analogs have entered the field, and cellular biochemistry has assumed a major role in our future progress. Although misonidazole has overall been a clinical failure, the investment in its laboratory and clinical study has opened up a whole new field of chemical modification based on sound biochemical principles.


Assuntos
Neoplasias/terapia , Protetores contra Radiação/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Reparo do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Glutationa/fisiologia , Humanos , Oxigênio/fisiologia
12.
Int J Radiat Oncol Biol Phys ; 39(4): 817-22, 1997 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9369128

RESUMO

PURPOSE: Many cancer chemotherapeutic agents interact with radiation to enhance the amount of radiation damage observed in both tumor and normal tissues. It is important to predict this interaction and to determine the effect of drug on sublethal damage repair. To evaluate for effects in rapid renewing normal tissues, the intestinal crypt cell in vivo assay is an excellent one to employ. These studies investigate the effect of eleven cancer chemotherapeutic drugs on split-dose repair in the intestinal crypt cell of the mouse. METHODS AND MATERIALS: LAF1 male mice, age 10-12 weeks, were exposed to whole-body irradiation with orthovoltage x-rays delivered as a single dose or as equally divided doses delivered with intervals between the two exposures of 2 to 24 h. In the experimental group, the cancer chemotherapeutic agent was administered intraperitoneally 2 h before the first radiation dose. At 3.6 days after the second irradiation, the mice were sacrificed; the jejunum was removed, fixed, and sectioned for light microscopy. The number of regenerating crypts were counted and corrected to represent the number of surviving cells per circumference. RESULTS: Of the eleven drugs tested, only carmustine eliminated split-dose repair. Cisplatin delayed repair, and methotrexate caused marked synchronization obliterating the observation of split-dose repair. CONCLUSIONS: Most cytotoxic chemotherapeutic agents do not inhibit sublethal damage repair in intestinal crypt cells when given 2 h before the first radiation exposure. Absence of the initial increase in survival seen with split-dose radiation is noted with carmustine and high-dose methotrexate.


Assuntos
Antineoplásicos/farmacologia , Jejuno/efeitos dos fármacos , Jejuno/efeitos da radiação , Cicatrização/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Fracionamento da Dose de Radiação , Esquema de Medicação , Infusões Parenterais , Masculino , Camundongos , Camundongos Endogâmicos , Irradiação Corporal Total
13.
Int J Radiat Oncol Biol Phys ; 19(3): 791-6, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2145249

RESUMO

High-dose-rate (HDR) remote afterloading intracavitary brachytherapy has been widely used in the treatment of carcinoma of the cervix in Europe and Asia since the 1960's. Recently, there has been an increase of interest in the use of this technique in North America. Most of the non-randomized studies suggest similar survival, local control, and complication rates using fractionated high-dose-rate remote afterloading intracavitary brachytherapy combined with external beam irradiation compared to historical or concurrent low-dose-rate (LDR) controls. However, the techniques as well as the dose fractionation schedules used in different institutions are variable. The optimal technique and dose fractionation scheme has yet to be established through systematic clinical trials.


Assuntos
Braquiterapia , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Metanálise como Assunto
14.
Int J Radiat Oncol Biol Phys ; 8(2): 279-82, 1982 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7085383

RESUMO

A total of 34 patients were studied in order to evaluate capsule vs. tablet form of misonidazole and intermittent vs. daily administration. These patients were given drug formulation of tablets for one week and capsules for one week on either an intermittent (1, 2, or 3 times per week) or daily schedule. Total doses ranged from 5-15 gm/m2. There was no significant difference seen in mean serum levels or half-lives between capsules and tablets. Daily misonidazole resulted in slight build-up of serum levels in the latter part of the week. There was no difference in toxicities seen with drug daily vs. intermittent administration.


Assuntos
Misonidazol/metabolismo , Nitroimidazóis/metabolismo , Adulto , Disponibilidade Biológica , Cápsulas , Esquema de Medicação , Avaliação de Medicamentos , Meia-Vida , Humanos , Misonidazol/administração & dosagem , Neoplasias/radioterapia , Comprimidos
15.
Int J Radiat Oncol Biol Phys ; 31(5): 1187-203, 1995 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-7713782

RESUMO

Toxicity of the respiratory system is a common side effect and complication of anticancer therapy that can result in significant morbidity. The range of respiratory compromise can extend from acute lethal events to degrees of chronic pulmonary decompensation, manifesting years after the initial cancer therapy. This review examines the anatomic-histologic background of the lung and the normal functional anatomic unit. The pathophysiology of radiation and chemotherapy induced lung injury is discussed as well as the associated clinical syndromes. Radiation tolerance doses and volumes are assessed in addition to chemotherapy tolerance and risk factors and radiation-chemotherapy interactions. There are a variety of measurable endpoints for detection and screening. Because of the wide range of available quantitative tests, it would seem that the measurement of impaired lung function is possible. The development of staging systems for acute and late toxicity is discussed and a new staging system for Late Effects in Normal Tissues (LENT) is proposed.


Assuntos
Pulmão/efeitos da radiação , Lesões por Radiação , Radioterapia/efeitos adversos , Protocolos Clínicos , Humanos , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/fisiopatologia , Lesões por Radiação/complicações , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/fisiopatologia , Tolerância a Radiação , Radiografia , Dosagem Radioterapêutica , Testes de Função Respiratória , Índice de Gravidade de Doença , Fatores de Tempo
16.
Int J Radiat Oncol Biol Phys ; 20(4): 761-9, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2004953

RESUMO

Neon ion radiotherapy possesses biologic and physical advantages over megavoltage X rays. Biologically, the neon beam reduces the oxygen enhancement ratio and increases relative biological effectiveness. Cells irradiated by neon ions show less variation in cell-cycle related radiosensitivity and decreased repair of radiation injury. The physical behavior of heavy charged particles allows precise delivery of high radiation doses to tumors while minimizing irradiation of normal tissues. In 1979 a Phase I-II clinical trial was started at Lawrence Berkeley Laboratory using neon ions to irradiate patients for whom conventional treatment modalities were ineffective. By the end of 1988 a total of 239 patients had received a minimum neon physical dose of 1000 cGy (median follow-up for survivors 32 months). Compared with historical results, the 5-year actuarial disease-specific survival (DSS5) and local control (LC5) rates suggest that neon treatment improves outcome for several types of tumors: a) advanced or recurrent macroscopic salivary gland carcinomas (DSS5 59%; LC5 61%); b) paranasal sinus tumors (DSS5 69%; LC5 69% for macroscopic disease); c) advanced soft tissue sarcomas (DSS5 56%, LC5 56% for macroscopic disease); d) macroscopic sarcomas of bone (DSS5 45%; LC5 59%); e) locally advanced prostate carcinomas (DSS5 90%; LC5 75%); and f) biliary tract carcinomas (DSS5 28%; LC5 44%). Treatment of malignant gliomas, pancreatic, gastric, esophageal, lung, and advanced or recurrent head and neck cancer has been less successful; results for these tumors appear no better than those achieved with conventional x-ray therapy. These findings suggest that Phase III trials using the neon beam should be implemented for selected malignancies.


Assuntos
Neônio/uso terapêutico , Neoplasias/radioterapia , Radioisótopos/uso terapêutico , Avaliação de Medicamentos , Humanos , Masculino , Radioterapia/efeitos adversos , Radioterapia/métodos , Estudos Retrospectivos
17.
Int J Radiat Oncol Biol Phys ; 27(1): 75-82, 1993 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8365945

RESUMO

PURPOSE: To determine the rates of survival and local control in patients with bile duct adenocarcinomas treated with post-operative photons and/or charged particles. METHODS AND MATERIALS: A retrospective study was performed analyzing all patients with bile duct adenocarcinomas who received radiotherapy through the University of California San Francisco and at Lawrence Berkeley Laboratory between 1977 and 1987, a total of 62 patients. University of California San Francisco patients received photon therapy (median dose 5400 cGy), and Lawrence Berkeley Laboratory patients were treated with the charged particles helium and/or neon (median dose 6000 cGyE). Forty-eight patients were treated post-operatively with curative intent, 30 with photons and 18 with particles. Thirty-six patients in the study had gross residual disease; none had microscopically negative margins. RESULTS: The overall two-year actuarial survival was 28%: 44% for particle-treated patients and 18% for patients treated with photons (p = .048). Median actuarial survival was 23 months in particle patients and 12 months in photon patients. Local control was also improved, though less significantly, in patients treated with particles (median disease-free survival 20 months vs. 4.5 months, p = .054). A univariate and multivariate analysis was performed and revealed that only extent of residual disease predicted local failure and overall survival; no other prognostic factors were identified. CONCLUSION: Compared to conventional photon radiotherapy, treatment with post-operative charged particle irradiation at Lawrence Berkeley Laboratory appeared to offer a survival advantage in this non-randomized series. Additional investigation into protection of surrounding normal tissue with better dose localization through the use of charged particles is planned.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias dos Ductos Biliares/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Feminino , Hélio , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neônio , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
18.
Int J Radiat Oncol Biol Phys ; 15(3): 703-10, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3138219

RESUMO

Little is known about radiosensitization produced by iododeoxyuridine (IUDR) with high linear energy transfer radiation. Likewise, the effect of IUDR on repair of sublethal or potentially lethal damage is unclear. A series of in vitro experiments was performed examining these aspects of IUDR radiosensitization. Human T1 cells were grown in the presence of 3.0 micromolar IUDR for 72 hours (approximately three doubling times), an exposure which resulted in minimal cytotoxicity to unirradiated cells. As the cells entered plateau phase they were exposed to X rays and a variety of heavy ion beams. Sensitization was found to decrease as linear energy transfer (LET) increased. No sensitization took place in an extremely high LET Lanthanum ion beam (1000 keV/micrometer). However, IUDR produced significant sensitization in the Neon ion beam currently used to treat cancer patients at Lawrence Berkeley Laboratory. Sensitization enhancement ratios at the 40% cell survival level were found to be 1.8 for X rays, 1.5 for the proximal Bragg peak of the clinical Neon beam, and 1.3 for the distal peak of the clinical Neon beam. Cell survival curves fitted to the linear-quadratic model showed IUDR significantly increased the value of the linear component (alpha) in beams with LETs below 40 keV/micron. The value of the quadratic component (beta) was unaffected by IUDR, regardless of LET. Split-dose experiments with both X rays and proximal peak Neon ions revealed IUDR did not affect sublethal damage repair. Similarly, delayed-plating experiments showed IUDR did not affect repair of potentially lethal damage. In contrast to cells unexposed to IUDR, IUDR-treated cells showed near-equal levels of cell killing throughout the extended Bragg peak of the clinical Neon beam. These findings suggest that the addition of IUDR to Neon ion radiotherapy could enhance the therapeutic ratio of the clinical Neon beam.


Assuntos
Idoxuridina/farmacologia , Tolerância a Radiação , Radiossensibilizantes , Radioterapia de Alta Energia , Sobrevivência Celular , Transferência de Energia , Humanos , Raios X
19.
Int J Radiat Oncol Biol Phys ; 41(5): 1099-111, 1998 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9719121

RESUMO

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Análise de Variância , Braquiterapia , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Lesões por Radiação/etiologia , Falha de Tratamento
20.
Int J Radiat Oncol Biol Phys ; 28(1): 257-61, 1994 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8270449

RESUMO

PURPOSE: Evaluate the use of helium charged particle radiotherapy in the treatment of residual or unresectable meningioma adjacent to critical structures. METHODS AND MATERIALS: Twenty-nine patients with meningioma of the skull base or spine were irradiated with helium charged particle radiotherapy at the University of California Lawrence Berkeley Laboratory (UCLBL) during the period 1981-1992. Twenty-six patients were treated for intracranial and three for spinal tumors. Total doses of 53.0-80.4 Gray equivalent (GyE) with a mean of 63 GyE were delivered using the helium ion beam. RESULTS: Ten-year local control and survival rates calculated by the Kaplan-Meier product limit method were 84% and 80% respectively. Doses of 60.0 GyE were delivered with a low rate of complications. The only failures were in massive, recurrent tumors. CONCLUSION: High doses using helium charged particle radiotherapy can be safely and effectively delivered to large residual or unresectable meningioma near radiosensitive structures.


Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Adulto , Idoso , Feminino , Hélio , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Aceleradores de Partículas , Radioterapia de Alta Energia , Taxa de Sobrevida
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