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Biomedical subjects

D Gonzalez Gonzalez

Publications and source records attributed to D Gonzalez Gonzalez.

18 recordsLinked to original sources
PubMed2000

Brachytherapy with transperineal (125)Iodine seeds for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer. PATIENTS AND METHODS: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy. RESULTS: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone. CONCLUSIONS: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.

Aged↗
PubMed1999

Long-term survival after resection of proximal bile duct carcinoma (Klatskin tumors).

This retrospective study in 79 surgically treated patients with a proximal bile duct carcinoma revealed 12 patients with a median age of 59.5 years (range 21-73 years) who survived more than 5 years. These 12 patients were analyzed to identify specific patient characteristics for long-term survival. Fifteen patients died from postoperative complications and were excluded from this survival analysis. In relation with preoperative Bismuth classification, there were 3 (20%) long-term survivors of 15 patients with type I tumors and 9 (35%) long-term survivors of 26 patients with type II tumors. In the group of type III and IV tumors, there were no long-term survivors. Concerning the type of resection, 9 of 51 (18%) patients had long-term survival after local resection and 3 of 13 (23%) patients after local resection combined with hemihepatectomy. Complete tumor-free surgical specimen margins were found in only 4 of 64 cases (6%), among which only one patient survived more than 5 years. Negative proximal bile duct margins, absence of multifocality, and diploid tumors showed a significant correlation with long-term survival. There was no significant correlation between long-term survival and postoperative radiotherapy. Of the 12 long-term survivors, 5 died after 5 years: 2 had developed metastases and 1 a local recurrence; the other 2 died of a metastasis of an ovarian adenocarcinoma and cachexia, respectively. The remaining seven patients were still alive at the completion of this study. The mean survival of the 64 patients analyzed in this study (in which hospital mortality was excluded) was 33.7 months, with a median survival of 18.8 months. In conclusion, the preoperative Bismuth classification of the tumor, absence of multifocality, diploid-type tumors, and negative proximal bile duct margins at histopathologic examination were the only significant prognostic factors for long-term survival.

Adult↗
PubMed1995

Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Adult↗
PubMed1993

Influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia.

The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally heated at a temperature of 45 degrees C (5-30 min). Loss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was significantly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cisplatin treated rats were more sensitive to heat than nerves from control rats (dose modifying factor = 1.5 +/- 0.2). Histopathological investigation of nerves after heat alone or after heat preceded by cisplatin confirmed these differences and showed that edema, vascular damage and axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies showed that cisplatin treatment before hyperthermia caused a delay in recovery from motor function loss of about 6 days. Cisplatin treatment after hyperthermia had no influence on recovery from motor function loss.

Animals↗
PubMed1992

Neurological complications after 434 MHz microwave hyperthermia of the rat lumbar region including the spinal cord.

Hyperthermia was applied in the region of the vertebral column from the second to the fifth lumbar vertebra using a ring-shaped 434 MHz microwave radiator. In all experiments temperatures were measured at a 'reference' thermocouple which was placed against the fourth lumbar vertebra. After 60 min of heat treatment at 'reference' temperatures of 43.0 degrees C, 44.0 degrees C and 45.0 degrees C (+/- 0.05 degrees C) the average maximal temperature inside the vertebral canal were 42.6 degrees C, 43.0 degrees C and 43.8 degrees C (+/- 0.3 degrees C), respectively. At all 'reference' temperatures the maximal core temperature of the animal did not exceed 40.5 +/- 0.3 degrees C after 60 min of heat treatment. Dorsal skin and muscle temperatures in the treatment area reached 'reference' temperature, and transient skin and muscle necrosis was observed after treatment for 1 h at 'reference' temperatures at 44 degrees C and 45 degrees C. Temperatures in the peritoneal cavity approximately 1 mm ventrally of the vertebral column rose to 41.8 degrees C after 60 min at reference 43.0 degrees C. Treatment at spinal cord temperature 42.6 degrees C for 60 min did not induce any significant neurological effects. Motoric dysfunction of the hind legs, such as difficulties with walking, was observed after 60 min treatment at spinal cord temperatures of 43.0 degrees C or 43.8 degrees C. In addition, 24 h after treatment at 43.8 degrees C for 60 min loss of tail tonus was observed, as well as loss of sensory function in the hind limbs. Recovery from the neurological disorders, except for the loss of tail tonus, occurred within 2 weeks after treatment. Histopathological examination revealed necrosis in the central areas of the spinal cord at 3 days and complete necrosis at 7 days after treatment at 43.8 degrees C for 60 min.

Animals↗
PubMed1991

Does additive radiotherapy after hilar resection improve survival of cholangiocarcinoma? An analysis in sixty-four patients.

Between September 1983 and January 1990, 64 patients with Klatskin tumors were treated with resective therapy in the Academic Medical Centre Amsterdam. Twenty-nine patients received postoperative adjuvant radiotherapy, 22 patients were treated with resective therapy only and there were 13 postoperative deaths. The longterm results in the patients treated with or without adjuvant radiotherapy were retrospectively assessed. Three patients had a curative resection. Comparison of both therapeutic modalities demonstrated a statistically significant difference in survival (P less than 0.001) in favour of the patients who were treated with additive radiotherapy. The radiotherapy was generally well tolerated.

Adenoma, Bile Duct↗
PubMed1991

External radiotherapy and extrahepatic bile duct cancer.

The hospital records of patients with extrahepatic bile duct cancer who where treated surgically between 1968 and 1983 were reviewed. Of 55 patients, 16 (29%) received radiotherapy after surgery. The total dose given ranged from 40 to 60 Gy. Median follow-up time for analysis was 4.0 months and lasted until January 1988. The overall median survival was 4 months (range 0-36), that of the irradiated patients was 16 months (range 2-36), and that of the 39 patients who were not irradiated was 3 months (range 0-32). When the 13 post operative deaths were excluded the median survival was 4 months. Radiotherapy did not cause any severe complications. No firm conclusion about the role of radiotherapy can be drawn from these data because the patients were not randomly chosen to receive radiotherapy and selection was therefore biased. We conclude that most patients with extrahepatic bile duct cancer still die of locoregional disease. Effective adjuvant treatments are needed and should be evaluated in prospective randomized trials.

Adenocarcinoma↗
PubMed1988

Chestwall recurrences of breast cancer: results of combined treatment with radiation and hyperthermia.

In 35 patients with chestwall recurrences of breast carcinoma, 45 lesions were treated with combined radiation and hyperthermia. The majority of the lesions received 6 fractions of 4 Gy, twice a week during 3 weeks. Hyperthermia was administered within 30 min after irradiation, aiming a tumor temperature of 43 degrees C during one hour. The percentage of complete response (CR) was 57%. In small lesions, the percentage of CR was 80%. The mean duration of the response was 7 months. Response rate increased with increasing temperature. Particularly, mean temperature and isoeffect thermal dose correlated very well with response rate. In nine cases, comparative lesions were treated with either radiation alone or radiation combined with hyperthermia. The response rates were 3/9 and 7/9, respectively. Acute skin reactions were enhanced by the combined treatment. However, late skin reactions were not increased. Although the prognosis of patients with chestwall recurrences is determined by the presence of distant metastases, local control remains an important objective. Combined treatment with radiation and hyperthermia offers the possibility of obtaining a high local control rate particularly in relatively small lesions.

Adult↗
PubMed1986

Combined treatment with radiation and hyperthermia in metastatic malignant melanoma.

In 24 patients with metastatic malignant melanoma, combined treatment with radiation and hyperthermia was administered to 38 localizations, radiation alone to 8 comparative localizations and hyperthermia alone to 3 localizations. Hyperthermia was administered during one hour by using a 433 MHz microwave generator. The heat treatment was given within 30 min following irradiation. Although an intratumoral temperature of 43 degrees C was aimed, considerable variations occurred during one session and from session-to-session. Radiation schedules consisted in either one large fraction (6-8 Gy) once a week in 14-21 days or two fractions (4-5 Gy) twice a week in 21 days. In the group of patients receiving irradiation once a week, three heat treatments were administered. In the twice-a-week radiation schedule, six heat sessions were given. The overall complete response (CR) rate in patients receiving combined treatment was 50%. In the group of patients treated with hyperthermia and irradiation schedules of 8 Gy per fraction, the CR rate was 83%. Irradiation alone achieved 38% CR rate but some of these CR relapsed during follow-up whereas the comparative area treated with radiation and heat remained under control at this time. The lesions treated with heat alone did not show any response to treatment. Enhancement of the acute skin reactions was generally observed. However, because the total doses were relatively low, this enhancement did not constitute a clinical problem. CR appears to occur more frequently in small tumor sizes. The highest and lowest temperature ever registered during any session of hyperthermia did not seem to correlate with the tumor response.

Combined Modality Therapy↗
PubMed1986

Radiotherapy with multiple fractions per day in pancreatic and bile duct cancer.

Twenty patients with pancreatic and bile duct cancer have been treated with external radiotherapy with multiple fractions per day (MFD). All patients had localized disease only. Sixteen patients have been treated with a split-course technique, to a dose of 60 to 70 Gy in 7-8 weeks, four patients had a continuous series of 44 Gy in 19 days. The mean survival was 7.9 months for patients with a pancreatic cancer. Four out of nine patients with pancreatic cancer in whom the tumour was evaluable showed a tumour regression, one out of nine reached a partial remission. The mean survival in the responders was 9.5 months. All patients with pancreatic cancer died of their tumour. Four out of eight patients with bile duct cancer died of their tumour, the mean survival was 10 months. Four patients with bile duct cancer are still alive (10+, 10+, 10+, 11+ months). No serious acute toxicity was seen. Six patients showed gastrointestinal toxicity at 1.5 to 9 months after the end of treatment. All of them could be treated in a conservative way. From the results obtained in this feasibility study, radiotherapy with MFD in pancreatic and bile duct cancer appears to achieve similar tumour response as conventionally fractionated radiotherapy and the observed toxicity of MFD can be considered as acceptable. MFD might be a more appropriate treatment scheme for combination with chemotherapy and radiosensitizers.

Adenocarcinoma↗
PubMed1983

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy.

A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with greater than 65 Gy, the two year local control was 35%. If treated with less than 65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was less than 100 cm2, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.

Adenocarcinoma↗
PubMed1982

Effects of irradiation by single or multiple fractions per day on transplantable murine mammary carcinoma.

Effects of different fractionation schedules of irradiation were studied in an experimental mammary adenocarcinoma transplanted in the back of mice. The number of fractions per day varied from one to three, keeping the daily dose constant. It was found that an increase of the number of fractions per day did not necessarily lead to a decrease in the tumour response, as might be expected for the same total dose. At a twelve-day overall time, three fractions per day did not give such a good result as one fraction per day, but at a nineteen-day overall time three fractions per day were about as good as one fraction per day; and below 45 Gy total dose, the result with three fractions per day even seemed to be better. The effects of actinomycin D administered during the irradiation treatment show that schedules with three fractions per day possibly take better advantage of repair of sublethal and potentially lethal damage than schedules with one fraction per day. Administration of misonidazole during the irradiation treatment led to a dose-modifying effect of 1.2 in one fraction per day schedules but had no significant effect in three fractions per day schedules. The present results may provide guidelines for clinical application of irradiation schedules with more than one fraction per day.

Adenocarcinoma↗
PubMedDate not supplied

Ultrastructural changes in the rat sciatic nerve after local hyperthermia.

The rat sciatic nerve was heated over a length of 5 mm for 30 min at 43, 44 or 45 degrees C. Morphological changes were not observed after heating at 43 degrees C. Treatment at 44 degrees C resulted in endoneurial oedema and mild vascular changes, such as contraction and vacuolization of endothelial cells and thickening of the media of the larger vessels. Within 1 week several demyelinated axons were observed. The first changes after heating at 45 degrees C included oedema, blood vessel occlusion and severe endothelial cell damage. Axonal changes, e.g. the accumulation of cell organelles, appeared 8 h after treatment; 24 h after treatment most axons and myelin sheaths showed degenerative changes. Absence of blood flow in the heated area of the nerve was shown 2 h after heating at 45 degrees C. We conclude that hyperthermic treatment directly affects endothelial cells and myelin sheaths in the rat sciatic nerve. Axons degenerate most probably as a consequence of ischaemia.

Animals↗
PubMedDate not supplied

Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology.

The ESHO protocol 3-85 is a multicentre randomized trial investigating the value of hyperthermia as an adjuvant to radiotherapy in treatment of malignant melanoma. A total of 134 metastatic of recurrent malignant melanoma lesions in 70 patients were randomized to receive radiotherapy alone (3 fractions in 8 days) or each fraction followed by hyperthermia (aimed for 43 degrees C for 60 min). Radiation was given with high voltage photons or electrons. Tumours were stratified according to institution and size (above or below 4 cm) and randomly assigned to a total radiation dose of either 24 or 27 Gy to be given with or without hyperthermia. The endpoint was persistent complete response in the treated area. A number of 128 tumours in 68 patients were evaluable, with an observation time between 3 and 72 months. Sixty-five tumours were randomized to radiation alone and 63 to radiation + heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was < or = 4 cm in 81 and > 4 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% versus rad + heat 46%, p = 0.008) and radiation dose (24 Gy 25% versus 27 Gy 56%, p = 0.02), but not of tumour size (small 42% versus large 29%, p = 0.21). A Cox multivariate regression analysis showed the most important prognostic parameters to be: hyperthermia (odds ratio: 1.73 (1.07-2.78), p = 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p = 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p = 0.05). Analysis of the heating quality showed a significant relationship between the extent of heating and local tumour response. Addition of heat did not significantly increase the acute or late radiation reactions. The overall 5-year survival rate of the patients was 19%, but 38% in patients if all known disease was controlled, compared to 8% in the patients with persistent active disease.

Adult↗
PubMedDate not supplied

Prognostic value of plasma transforming growth factor-beta in patients with glioblastoma multiforme.

We investigated whether the postoperative concentration of circulating transforming growth factor beta (TGF-beta) yields prognostic value in patients with glioblastoma multiforme (gbm). Blood was collected from 20 healthy volunteers and in 28 patients with mainly glioblastoma multiforme (gbm), both before radiotherapy, during and after 4 weeks of irradiation. Both latent and active TGF-beta were quantified directly in the blood plasma using a bioassay with mink lung epithelial cells transfected with a plasminogen activator inhibitor-1 promotor luciferase construct. The average plasma concentration of TGF-beta before radiotherapy for gbm patients was 26.2 ng/ml, which was significant higher than in normal controls (16.2 ng/ml, p=0.02). No correlation was found between TGF-beta and survival, nor between plasma TGF-beta and the diameter of the postoperative contrast-enhancing lesion. The pattern of plasma TGF-beta during radiotherapy did not correlate with the clinical course of patients, nor with the fractionation scheme. Plasma TGF-beta did not reveal a clinical useful prognostic value for gbm patients, which is partly due to the large variation in TGF-beta plasma levels between individual patients.

Aged↗