RESUMEN
PURPOSE: To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer. MATERIALS AND METHODS: Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted. RESULTS: In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005). CONCLUSION: Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.
Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Flutamida/efectos adversos , Neoplasias de la Próstata/terapia , Anciano , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Aspartato Aminotransferasas/sangre , Pruebas Enzimáticas Clínicas , Estudios de Cohortes , Terapia Combinada , Flutamida/uso terapéutico , Enfermedades Gastrointestinales/inducido químicamente , Goserelina/uso terapéutico , Humanos , Pruebas de Función Hepática , Masculino , Estudios Prospectivos , Dosificación RadioterapéuticaRESUMEN
PURPOSE: To review the experience at University of California Lawrence Berkeley Laboratory in using charged particles to irradiate primary neoplasms of the skull base and those extending to the skull base from the nasopharynx and paranasal sinuses. METHODS AND MATERIALS: During the period from 1977 to 1992, 223 patients were irradiated with charged particles at the Lawrence Berkeley Laboratory for tumors either arising in or extending to the skull base, of whom 48 (22%) had recurrent lesions, either post previous surgery or radiotherapy. One hundred twenty-six patients had lesions arising in the cranial base, mostly chordoma (53), chondrosarcoma (27), paraclival meningioma (27) with 19 patients having other histologies such as osteosarcoma or neurofibrosarcoma. There were also 31 patients with primary or recurrent squamous carcinoma of the nasopharynx extending to the skull base, 44 patients with major or minor salivary gland tumors, mostly adenocarcinoma, and 22 patients with squamous carcinoma of the paranasal sinuses, all with cranial base extension. RESULTS: Local control and survival appeared improved in tumors arising in the skull base, following the ability with charged particles to deliver high doses (mean of 65 Gy-equivalent) with relative sparing of the adjacent normal tissues. The Kaplan-Meier 5-year local control was 85% for meningioma, 78% for chondrosarcoma, 63% for chordoma and 58% for other sarcoma. Follow-up ranged from 4-191 months with a median of 51 months. CONCLUSION: Charged particle radiotherapy is highly effective in controlling cranial base lesions which have have been partially resected. Better tumor localization with CT and MRI, improved 3-D treatment planning and beam delivery techniques have continued to reduce the level of serious complications and increase local control and survival.
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Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias Craneales/radioterapia , Femenino , Helio , Humanos , Iones , Masculino , Neón , Radioterapia de Alta EnergíaRESUMEN
Between 1976 and 1987, 52 patients with tumors adjacent to and/or involving the cervical, thoracic, or lumbar spinal cord were treated with charged particles at the University of California Lawrence Berkeley Laboratory. The histologies included chordoma and chondrosarcoma (24 pts), other bone and soft tissue sarcoma (14 pts), and metastatic or unusual histology tumors (14 pts). Radiation doses ranged from 29 to 80 Gray-equivalent (GyE), with a median dose of 70 GyE. Twenty-one patients received a portion of their treatment with photons. Median followup was 28 months. For 36 previously untreated patients, local control was achieved in 21/36 patients and the 3-year actuarial survival was 61%. Of 16 patients treated for recurrent disease, 7/16 were locally controlled and the 3-year actuarial survival was 51%. For patients treated for chordoma and chondrosarcoma, probability of local control was influenced by tumor volume (less than 100 cc or greater than 150 cc) and whether disease was recurrent or previously untreated. Complications occurred in 6/52 patients, including one spinal cord injury, one cauda equina and one brachial plexus injury, and three instances of skin or subcutaneous fibrosis. Charged particle radiotherapy can safely deliver high tumor doses to paraspinal tumors with good local control.
Asunto(s)
Condrosarcoma/radioterapia , Cordoma/radioterapia , Radioterapia de Alta Energía , Neoplasias de la Médula Espinal/radioterapia , Adolescente , Adulto , Anciano , Niño , Condrosarcoma/epidemiología , Condrosarcoma/mortalidad , Cordoma/epidemiología , Cordoma/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Neoplasias de la Médula Espinal/epidemiología , Neoplasias de la Médula Espinal/mortalidad , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Tronco Encefálico , Glioma/radioterapia , Adulto , Estudios de Seguimiento , Humanos , Radioterapia/métodos , Dosificación RadioterapéuticaRESUMEN
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.
Asunto(s)
Neón/uso terapéutico , Neoplasias/radioterapia , Radioisótopos/uso terapéutico , Evaluación de Medicamentos , Humanos , Masculino , Radioterapia/efectos adversos , Radioterapia/métodos , Estudios RetrospectivosRESUMEN
Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075).
Asunto(s)
Helio/uso terapéutico , Melanoma/radioterapia , Melanoma/secundario , Radioterapia de Alta Energía , Neoplasias de la Úvea/radioterapia , Análisis Actuarial , Femenino , Humanos , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.
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Cuerpo Ciliar , Melanoma/radioterapia , Neoplasias de la Úvea/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Glaucoma Neovascular/etiología , Helio , Humanos , Iones , Melanoma/mortalidad , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Aceleradores de Partículas , Radioterapia de Alta Energía , Tasa de Supervivencia , Neoplasias de la Úvea/mortalidadRESUMEN
During the period 1977 to 1985, 12 patients with FIGO stage II and III epithelial ovarian carcinoma failed to achieve a pathologic complete response with chemotherapy and underwent salvage whole-abdominal irradiation (WAXRT). Six of these patients had gross residual disease present at the time of irradiation, and three (50%) were unable to complete the planned radiotherapy. All eventually failed in the treatment field; their 5-year actuarial survival and local control rates were zero. The other six were irradiated without residual macroscopic disease. Five of the six (83%) were able to complete WAXRT as planned without prolonged delays. The 5-year actuarial survival and local control rates for this group were 21 and 25%, respectively. The actuarial laparotomy rate to relieve bowel obstruction following WAXRT was 40% at 2 years. The results from this and other series indicate that salvage WAXRT is not effective for patients irradiated with macroscopic tumor. However, WAXRT appears to be potentially curative for a small but significant percentage of patients irradiated without gross disease, although the risk of significant complications is high.
Asunto(s)
Carcinoma/terapia , Neoplasias Ováricas/terapia , Abdomen , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma/radioterapia , Terapia Combinada , Epitelio , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/radioterapia , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
During the 30 year period from 1957 to 1986, 42 patients with primary tumors arising from the spinal cord or cauda equina received postoperative irradiation at the University of California, San Francisco. Twenty-one patients had ependymomas: 18 were localized to one site, and 3 diffusely involved the cord. There were 12 patients with low grade astrocytomas and 3 with highly anaplastic astrocytoma or glioblastoma multiforme. All astrocytomas were localized at presentation. In 6 cases tissue was insufficient to permit a histologic diagnosis. Thirty-nine patients (93%) received total radiation doses ranging between 45.0-54.7 Gy using standard fractionation. The 10-year actuarial disease-specific survival rate for patients with localized ependymoma was 93%; 33% of these tumors recurred locally. The corresponding rate for diffuse ependymomas was 50%; the spinal disease was controlled in all 3 patients, but one developed a cerebral metastasis despite prophylactic cranial irradiation. Low-grade astrocytoma patients had a 10-year actuarial disease-specific survival rate of 91%, with 33% of these tumors recurring locally. No patient with highly anaplastic astrocytoma or glioblastoma multiforme survived longer than 8 months; all of these tumors recurred locally, and two of the three also developed diffuse craniospinal axis metastases. Local recurrence for ependymoma was delayed as long as 12 years following treatment, while all but one astrocytoma failure occurred within 3 years of treatment. No significant dose-response relationship with respect to local control was noted for either localized ependymomas or low grade astrocytomas. One patient developed radiation myelitis after receiving 50.4 Gy with standard fractionation. These results indicate that patients who undergo postoperative irradiation for low grade spinal astrocytomas and localized spinal ependymomas achieve excellent survival. However, despite treatment with total radiation doses taken to the practical limit of spinal cord tolerance, local failure remains common.