RESUMEN
PURPOSE: To determine the potential advantage of androgen ablation following standard external-beam radiation therapy in patients with locally advanced (clinical or pathologic T3; clinical or pathologic node positive) carcinoma of the prostate. METHODS AND MATERIALS: In 1987 the RTOG initiated a Phase III trial of long-term adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients were accrued to the study of which 945 remain analyzable: 477 on the adjuvant hormone arm (Arm I); and 468 on the radiation only arm (Arm II) with hormones initiated at relapse. The initial results were reported in the Journal of Clinical Oncology in 1997. RESULTS: With a median follow up of 5.6 years for all patients and 6.0 years for living patients local failure at 8 years was 23% for Arm I and 37% for Arm II (p < 0.0001). Distant metastasis was likewise favorably impacted with the immediate use of hormonal manipulation with a distant metastasis rate in Arm I of 27% and 37% in Arm II (p < 0.0001). Disease-free survival (NED survival) and NED survival with PSA of 1.5 ng/mL (bNED) or less were both statistically significant in favor of the immediate hormone arm (both p < 0.0001). Cause-specific failure was not statistically different with a cause-specific failure of 16% for Arm I and 21% in Arm II (p = 0.23). Overall survival was likewise not statistically different between two arms, with a 49% overall survival at 8 years in Arm I and 47% in Arm II (p = 0.36). Subset analysis of centrally reviewed Gleason 8-10 patients who did not undergo prostatectomy showed that for patients receiving radiation therapy plus adjuvant hormones there was a statistically significant improvement in both absolute (p = 0.036) and cause-specific survival (p = 0.019). CONCLUSIONS: Use of long-term adjuvant androgen deprivation in addition to definitive radiation therapy results in a highly significant improvement in regards to local control, freedom from distant metastasis, and biochemical free survival in unfavorable prognosis patients with carcinoma of the prostate.
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Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Goserelina/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Pronóstico , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/patología , Dosificación Radioterapéutica , Análisis de Supervivencia , Insuficiencia del TratamientoRESUMEN
This report describes two patients who developed persistent neurologic deficits during intracranial EEG recording without clear evidence of intracranial edema or infarction. Both patients had previously received high-dose brain radiation therapy and chemotherapy. Because of this experience, we strongly caution the use of intracranial electrodes in patients with similar profiles.
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Antineoplásicos/efectos adversos , Encefalopatías/etiología , Electrodos Implantados/efectos adversos , Electroencefalografía/métodos , Epilepsia/diagnóstico , Radioterapia/efectos adversos , Adulto , Encefalopatías/inducido químicamente , Encefalopatías/diagnóstico , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/radioterapia , Diagnóstico Diferencial , Electroencefalografía/estadística & datos numéricos , Epilepsia/epidemiología , Humanos , Imagen por Resonancia Magnética , Masculino , Grabación de Cinta de VideoRESUMEN
PURPOSE: Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS: In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS: Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION: Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos Hormonales/uso terapéutico , Goserelina/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Quimioterapia Adyuvante , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Análisis de SupervivenciaRESUMEN
Superficial hyperthermia with present day applicators provides a challenge when tumours exceed several cm in diameter. Unless microstrip applicators are scanned, the usable heat region often falls short of treating the entire region with 50% power or specific absorption rate (SAR). New microstrip applicator designs were evaluated through SAR analysis and compared to the traditional microstrip applicators used in the clinic at Dartmouth over the past six years. The new designs included fabricating thin archimedean spirals (1.0 mm strip width) incorporating dielectric substrate (epsilon = 5.3-10.8). The designs were optimized at 433 MHz for an arm length of 59 cm. Measurements in a plane 1.0 cm from the surface showed that thin spirals outperformed traditional designs by increasing the 50% SAR area by a factor of 2.5, while maintaining the same physical size. Arrays of four elements were fabricated from thin spirals, although SAR evaluation showed only 10-20% SAR between elements. Since this was deemed unacceptable and the design goal was to fabricate a stationary applicator that had at least 50% SAR between elements, dual element designs were created with gradually overlapped elements. It was found that overlapping three coils of the spiral created a large region that equalled or exceeded 50% SAR that could not be matched by single applicators. Coherent operation of the dual spiral array resulted in more central power deposition and incoherent operation resulted in more peripheral power deposition. SAR measurements at the fat/muscle interface showed an elongated heating pattern in hydroxyethylcellulose muscle equivalent phantom. Power deposition 1.0 cm deep in muscle retained the same basic size and shape with or without the fat layer. Patient treatments for chestwall tumours confirmed that the dual overlapping applicator heated a larger region without the sharp temperature peak associated with single applicators.
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Neoplasias de la Mama/terapia , Hipertermia Inducida/instrumentación , Tejido Adiposo , Impedancia Eléctrica , Femenino , Humanos , Microondas , Músculo Esquelético , TemperaturaRESUMEN
PURPOSE: Microwave antennas of various designs were inserted into arrays of nylon catheters implanted in brain tumors with the goal of raising temperatures throughout the target volume to 43.0 degrees C. METHODS AND MATERIALS: All antennas were flexible, and included dipole, choke dipole, modified dipole, and helical designs driven at 915 or 2450 MHz. Antennas were tested in brain-equivalent phantom in arrays. Phase shifting and phase rotation techniques were incorporated into the treatment system to steer power in the tumor, assisted by a treatment planning computer that predicted power deposition patterns and temperature distributions. Choke antennas were designed and tested to reduce a dependence of the central power location on depth of insertion into tissue. Temperature data analysis used only central and orthogonal axes mapping data measured at 2.0 mm intervals. RESULTS: A total of 23 patients were treated, using from one to six microwave antennas. Minimum tumor temperatures, averaged over the 60 min treatment, ranged from 37.2-44.3 degrees C (mean 40.0 degrees C) and maximum average tumor temperatures ranged from 46.5-60.1 degrees C (mean 49.1 degrees C). The percentage of all measured temperatures reaching therapeutic levels (> or = 43.0 degrees C) was 70.9. T90, the temperature at which 90% of all measured temperatures equaled or exceeded, was 40.8 degrees C, and T50 was 44.2 degrees C. CONCLUSION: Patient data analysis showed that the array of four dipole antennas spaced 2.0 cm apart were capable of heating a volume of 5.9 cm (along the central array axis) x 2.8 cm x 2.8 cm.
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Neoplasias Encefálicas/terapia , Hipertermia Inducida/métodos , Microondas , Humanos , Terapia Asistida por Computador/métodosRESUMEN
Combined therapies of cisplatin and radiation have resulted in clinical reports of apparent efficacious control of locoregional cancer and enhanced survival. Mechanisms of interaction between platinum and radiation that may explain these clinical observations all have in common the prediction that higher concentrations of platinum in all tumor cells close in time to irradiation should lead to greater potentiation of radiation-induced killing of those cells. Cisplatin is thus viewed as providing some radiation-equivalent, or a radiation dose-effect factor, for sterilization of tumors. One disease site that has not been well investigated for response to cisplatin plus radiation therapy, but that could benefit from it, is locally advanced prostate cancer. A body of literature now supports the view that local control of stage C (T3, N0, M0) prostate cancer is correlated with disease-free survival. This correlation makes prostate cancer a candidate for potentially achieving improved cure rates following local tumor sterilization by combining cisplatin with radiation therapy. The need and approaches to optimize delivery of cisplatin within tumor tissue is explored. Increasing cisplatin concentration to all the cells of a tumor, i.e., homogeneously delivering systemic high-dose cisplatin, should benefit the efficacious response otherwise expected for cisplatin combined with radiation. Strategies to increase the homogeneity of cisplatin delivery to a tumor are considered to be those that increase perfusion to that tumor. Vasoactive agents used in anticancer protocols are especially considered for their potential value in serving to increase tumor perfusion. These protocol-inclusive agents include certain cytokines and L-arginine antagonists, and should be better managed and accepted in practice compared to other vasoactive agents that need to be developed as specific additives to protocol designs.
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Cisplatino/uso terapéutico , Neoplasias de la Próstata/terapia , Aminoácido Oxidorreductasas/metabolismo , Animales , Arginina/antagonistas & inhibidores , Línea Celular , Cisplatino/farmacocinética , Terapia Combinada , Humanos , Masculino , Óxido Nítrico Sintasa , Próstata/metabolismo , Dosificación RadioterapéuticaRESUMEN
Interstitial microwave hyperthermia in combination with iridium-192 brachytherapy has been administered to 23 cases of malignant brain tumours in a phase one clinical trial to assess the feasibility and safety of this treatment. In order to quantify the acute and long-term response of tumour and surrounding brain to this treatment, a morphometric computed tomography scan analysis was performed in 18 evaluable patients. Volumes defined by the outer margin of the contrast-enhancing rim, by the hypodense necrotic region within the enhancing rim and by the surrounding hypodensity region were calculated from computer measurements. Hyperthermia equipment performance (HEP) was calculated for the evaluation of heating. After the treatments, the volume of the inner hypodensity region decreased in seven patients and the volume increased in 11 patients. In five patients, the outer margin of the contrast-enhancing lesion showed an initial increase in volume followed by a decrease and in these patients higher HEP and longer survival were observed significantly. The volume of the surrounding hypodensity region varied following treatments, but in most instances, the region subsequently increased in the interval immediately prior to death. Contribution of heat effect to these changes are discussed and the significance of aggressive heating, which provides transient opening of blood brain barrier, is shown.
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Braquiterapia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/terapia , Hipertermia Inducida , Adulto , Anciano , Astrocitoma/diagnóstico por imagen , Astrocitoma/radioterapia , Astrocitoma/terapia , Barrera Hematoencefálica , Neoplasias Encefálicas/diagnóstico por imagen , Terapia Combinada , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/radioterapia , Glioblastoma/terapia , Humanos , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/métodos , Radioisótopos de Iridio/uso terapéutico , Masculino , Melanoma/radioterapia , Melanoma/secundario , Melanoma/terapia , Microondas/efectos adversos , Microondas/uso terapéutico , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Benign prostatic hyperplasia (BPH) is a common disease of elderly men. The current definitive treatment for urinary obstruction caused by this disease is surgery (transurethral resection of the prostate, or TURP). Recent evidence suggests that hyperthermia may be a useful nonsurgical alternative for treatment of symptomatic BPH. A transurethral microwave applicator has been designed around a Foley catheter for delivery of local hyperthermia to the prostate. The Foley balloon is used to maintain the antenna position within the prostatic urethra. The Foley catheter also features an antenna choke to confine power deposition to the intended region. The antenna is a coaxial dipole designed to operate at 915 MHz. Qualitative and quantitative specific absorption rate (SAR) patterns are shown for this antenna. In vivo experiments in dog prostate demonstrate that temperatures > 42 degrees C can be obtained > 1 cm away from the catheter, while maintaining a maximum urethral temperature of 47 degrees C to 48 degrees C. Histology obtained acutely after the hyperthermia treatments showed minimal damage to the periurethral tissues. We conclude from these studies that this microwave applicator is capable of providing local hyperthermia to the prostatic tissues with a predictable and well-circumscribed thermal distribution.
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Hipertermia Inducida/instrumentación , Próstata/fisiología , Hiperplasia Prostática/terapia , Animales , Temperatura Corporal , Perros , Diseño de Equipo , Humanos , Hipertermia Inducida/métodos , Masculino , Matemática , Microondas , Modelos Teóricos , UretraRESUMEN
Over the course of 3 years, tumours of 19 patients were heated with ultrasound in the operating room during surgical resection. Immediately following intraoperative radiation therapy, thermocouples were inserted into tumour and adjacent normal structures. Patients were then given a 60-min heat treatment with ultrasound after a 10-15-min heatup period. Temperatures were measured at a total of 133 fixed locations for the 19 patient series. Temperature mapping was done in the tumour volume when logistically feasible. Treatment sites included colorectal (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3), sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating system was utilized to control surface temperatures. Three generations of completely immersible transducers were designed over the course of this study with a 4-cm height specification. Since the ultrasound transducer was assembled on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic field to the tumour size. Average of the maximum temperatures attained was 46.6 degrees C. Temperature with which 90% of all measured points equalled or exceeded (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient clinic series, in which superficial tumours were treated with a similar external applicator, and patient tolerance was often a treatment limitation.
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Hipertermia Inducida/métodos , Neoplasias/terapia , Terapia por Ultrasonido/métodos , Terapia Combinada , Estudios de Evaluación como Asunto , Humanos , Hipertermia Inducida/instrumentación , Periodo Intraoperatorio , Neoplasias/cirugía , Termómetros , Transductores , Terapia por Ultrasonido/instrumentaciónRESUMEN
In a phase I clinical study, 10 patients with obstructive biliary carcinomas were treated with single-antenna interstitial microwave hyperthermia and iridium-192 brachytherapy. For each patient a standard biliary drainage catheter was implanted percutaneously through the obstructed common bile duct. This catheter accommodated a single microwave antenna which operated at 915 MHz, and one or two fibreoptic thermometry probes for temperature measurement. Under fluoroscopic guidance the microwave antenna and temperature probes were positioned in the CT-determined tumour mass. The 60-min heat treatment achieved a central tumour temperature of 45-55 degrees C while keeping temperatures at the proximal and distal margins at 43 degrees C. Immediately following the hyperthermia treatment the microwave antenna and temperature probes were removed, and a single strand of iridium-192 double-strength seeds was inserted to irradiate the tumour length. A dose of 5500-7900 cGy calculated at 0.5 cm radially from the catheter was administered over 5-7 days. Upon removal of the iridium a second hyperthermia treatment was performed. A total of 18 hyperthermia treatments were administered to the 10 patients. In two cases the second hyperthermia treatment after brachytherapy was not possible due to a kink in the catheter, or bile precipitation in the catheter. All patients tolerated the procedure well, and there were no acute complications. To evaluate the volumetric heating potential of this hyperthermia method, specific absorption rate (SAR) values were measured at 182 planar points in muscle phantom. Insulated and non-insulated antenna performance was tested at 915 MHz in a biliary catheter filled with air, saline, or bile to mimic clinical treatments. The insulated antenna exhibited the best performance. Differences between antenna performance in saline and bile were also noted. In summary, this technique may have potential for tumours which obstruct biliary drainage and are accessible to percutaneous decompression using standard diagnostic radiological procedures.
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Neoplasias del Sistema Biliar/terapia , Hipertermia Inducida , Radioisótopos de Iridio/uso terapéutico , Neoplasias del Sistema Biliar/complicaciones , Neoplasias del Sistema Biliar/radioterapia , Braquiterapia , Colestasis Extrahepática/etiología , Colestasis Extrahepática/radioterapia , Colestasis Extrahepática/terapia , Terapia Combinada , Humanos , Microondas/uso terapéutico , Modelos Estructurales , TemperaturaRESUMEN
The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.
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Cisplatino/uso terapéutico , Histiocitoma Fibroso Benigno/terapia , Hipertermia Inducida , Neoplasias de los Tejidos Blandos/terapia , Anciano , Cisplatino/farmacocinética , Terapia Combinada , Antebrazo , Histiocitoma Fibroso Benigno/tratamiento farmacológico , Histiocitoma Fibroso Benigno/metabolismo , Humanos , Masculino , Platino (Metal)/farmacocinética , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/metabolismo , Distribución TisularRESUMEN
A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.
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Braquiterapia/instrumentación , Diatermia/instrumentación , Neoplasias Vaginales/terapia , Neoplasias de la Vulva/terapia , Diseño de Equipo , Estudios de Evaluación como Asunto , Femenino , Humanos , Neoplasias Vaginales/radioterapia , Neoplasias de la Vulva/radioterapiaRESUMEN
A planar ultrasound transducer was modified by etching concentric circles on one surface of a piezoelectric ceramic to create four rings. The 10 cm diameter transducer had four active rings and an unenergized centre. The transducer housing was designed to be completely immersed in fluid, suitable for intraoperative hyperthermia. The transducer was resonant at 1.0 MHz and was tested in a water tank and in an acoustic absorbing medium where the steady-state temperatures were measured. A comparison between a single 10 cm element and the concentric ring modification with all rings at equal power density showed the performance to be nearly identical. In vivo experiments in canine thigh verified the phantom predictions as individual rings were energized. Theoretical intensity calculations were made and compared favourably to water tank test results. Clinical hyperthermia treatments for chest wall and head and neck tumours showed that the temperature distribution could be highly modified by adjusting the power to individual rings while holding the transducer stationary. Automated temperature mapping parallel to the transducer face was used to compare a single element applicator to the concentric ring applicator in clinical treatments on the same lesion. The concentric ring applicator was radially adjustable and was found to be advantageous in lowering the central peak temperatures and flattening the temperature distribution in tumours. A comparison between the single element clinical and operating room series showed that when pain is removed as a treatment limiting factor, higher central tumour temperatures are possible and more of the tumour volume achieves therapeutic temperatures. The concentric ring design improves the temperature distribution such that the higher central temperatures will not be necessary.
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Hipertermia Inducida/instrumentación , Neoplasias/terapia , Terapia por Ultrasonido/instrumentación , Estudios de Evaluación como Asunto , Humanos , Control de Calidad , Temperatura , TermómetrosRESUMEN
An experimental canine brain model was developed to assess the effects of hyperthermia for a range of time and temperature endpoints, delivered within a specified distance of an interstitial microwave antenna in normal brain. The target temperature location was defined radially at 5.0 or 7.5 mm from the microwave source at the longitudinal location of maximum heating along the antenna in the left cerebral cortex. Temperatures were measured with fiberoptic probes in a coronal plane at this location in an orthogonal catheter at 1.0 mm intervals. Six antennas were evaluated, including dipole, modified dipole, and four shorted helical antennas with coil lengths from 0.5 to 3.9 cm. Antenna performance evaluated in tissue equivalent phantom by adjusting frequency at a fixed insertion depth of 7.8 cm or adjusting insertion depth at 915 MHz showed dipoles to be much more sensitive to insertion depth and frequency change than helical antennas. Specific absorption rate (SAR) was measured in a brain/skull phantom and isoSAR contours were plotted. In vivo temperature studies were also used to evaluate antenna performance in large and small canine brain tissues. A helical antenna with a 2.0 cm coil length driven at 915 MHz was chosen for the beagle experiments because of tip heating characteristics, well-localized heating along the coil length, and heating pattern appropriate to the smaller beagle cranial vault. Verification of lesion dimensions in 3-D was obtained by orthogonal MRI scans and histology to document the desired heat effect, which was to obtain an imagable lesion with well-defined blood-brain-barrier breakdown and necrotic zones. The desired lesion size was between 1.5 to 2.5 cm diameter radially, in the coronal plane with the greatest diameter.
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Encéfalo/anatomía & histología , Hipertermia Inducida/métodos , Animales , Encéfalo/patología , Encéfalo/fisiología , Perros , Hipertermia Inducida/instrumentación , Imagen por Resonancia Magnética , Modelos Anatómicos , Cráneo/anatomía & histologíaRESUMEN
RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms.
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Melanoma/radioterapia , Neoplasias Cutáneas/radioterapia , Adolescente , Adulto , Anciano , Estudios de Evaluación como Asunto , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Estudios Prospectivos , Dosificación Radioterapéutica , Neoplasias Cutáneas/patología , Factores de TiempoRESUMEN
Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic "bath" plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2.
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Neoplasias Ováricas/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Terapia Combinada , Creatinina/sangre , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Traumatismos por Radiación/epidemiologíaRESUMEN
We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide Aguda/cirugía , Adolescente , Adulto , Células de la Médula Ósea , Separación Celular , Ensayo de Unidades Formadoras de Colonias , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Controlled experiments have shown that more than one mechanism leads to the potentiation of radiation-induced cell killing by cisplatin, and that this potentiation is not uniformly expressed among different cell types. A firm investigative base for the design of clinical trials using cisplatin and radiation has not been established. Coincident with this deficiency of experimental guidance, the independent clinical investigator has developed an array of therapeutic strategies applying different doses and sequences of cisplatin and radiation to a variety of tumor types. Results of clinical studies integrating cisplatin and radiation that can be judged for perceived survival benefit are evaluated in comparison with existing radiobiologic information. Both the clinical and radiobiologic results lead to similar conclusions at this time. Cells that are relatively sensitive to the cytotoxic action of cisplatin alone would best be considered for combined treatment with radiation. Large and infrequent, rather than small and frequent, individual administrations of cisplatin are better used with radiation for enhanced therapeutic effectiveness. Administration of cisplatin close in time to radiation is best for therapeutic response, although perceived efficacy follows from rather flexible integrations of these two modalities. It is not possible to know if clinical efficacy results from radiation potentiation as opposed to some degree of additivity of the two modalities. It is nonetheless useful to anticipate strategies that might lead to radiation potentiation by cisplatin in therapeutic designs. Two general mechanisms by which cisplatin potentiates radiation-induced cell killing are identified. One mechanism of potentiation is free radical-mediated, at least in part leads to an active radiolytic species following one-electron reduction of cisplatin, and is more readily expressed with bacterial cells than with mammalian cells in tissue culture. A second mechanism of potentiation is biochemical in nature, involves an effect of cisplatin on cellular components in ways that inhibit the recovery of radiation-induced damage, and likely applies more to the potentiation of oxic mammalian cells than bacterial cells. The latter mechanism is not universally supported in the literature. However, a unifying hypothesis, and one in need of confirmation at this time, is that the biochemical mechanism of radiation potentiation by cisplatin operates in oxic mammalian cells that are inherently sensitive to the cytotoxic action of cisplatin. This hypothesis ostensibly applies to tumor cells that are responsive to chemotherapy with cisplatin.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias/radioterapia , Compuestos Organoplatinos/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Animales , Carboplatino , Cisplatino/farmacología , Terapia Combinada , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
The more recent engineering and clinical aspects of interstitial hyperthermia are reviewed. The advantages and difficulties of microwave, radiofrequency, and ferromagnetic seeds are evaluated and some future directions for improvements are outlined.