Is concurrent twice-daily thoracic radiotherapy with chemotherapy the reference treatment for small cell lung cancer?
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Biomedical subjects
Publications and source records attributed to P Van Houtte.
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The relationship between cell pigmentation and radiosensitivity was investigated in two selected human melanoma cell lines with different melanin content (mixed type: eumelanin and pheomelanin, and pheomelanotic phenotypes). The same study was also done after stimulation of melanogenesis (1) by addition of the melanin precursor l-tyrosine to each of the cell lines separately and (2) by irradiation alone with doses ranging from 0 to 10 Gy. We found that a decrease in cell radiosensitivity was correlated with the type of melanin, with a clear involvement of eumelanin rather than pheomelanin. Increasing the intracellular content of both melanins promoted the growth of irradiated cells. Moreover, at a dose of 10 Gy, both tyrosinase activity and melanin cell content were significantly increased in the absence of any other melanogenesis promoter. Our data suggest that the amount of intracellular melanin is inversely related to the radiosensitivity of melanoma cells and may explain at least in part the controversial responses to ionizing radiations reported for melanoma.
OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.
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PURPOSE: The objective of this work is to investigate the role of radiation therapy in the treatment of primary tracheal carcinoma. METHODS AND MATERIALS: From 1963 to 1993, 106 patients presenting with a tracheal carcinoma received a radiation course as part of their treatment in three institutions. Eighty-four patients were treated with megavoltage radiation only, receiving doses ranging from 30 to 70 Gy, with a median dose of 56 Gy. Five patients received high-dose-rate (HDR) brachytherapy, five patients underwent a surgical procedure, and eight received chemotherapy. RESULTS: With a mean follow-up of 141 months, the overall 1-, 2-, and 5-year survival rates are 46%, 21%, and 8%, respectively. Prognostic factors included tumor size (less than 3 cm), performance status, and total radiation dose: the 5-year survival rate dropped from 12% for patients receiving doses greater than 56 Gy to 5% for lower doses. Performance status and radiation doses are the only independent significant factors in multivariate analysis; these results must however be analyzed with precaution in this retrospective study. CONCLUSIONS: Radiation is a good alternative to surgery for primary tracheal cancer. A review of the literature and our current results allow us to recommend a radiation dose greater than 60 Gy for primary irradiation. Collaborative studies are warranted to (1) determine the optimal radiation dose for definitive irradiation, (2) define the potential role of radiation after complete and partial surgery, (3) determine the role and optimal treatment scheme for HDR brachytherapy, (4) describe and record the late effects, (5) establish the potential benefit of chemoradiation.
The side-effects of radiation therapy on the bronchial tree or on the mediastinum are seldom reported. In this setting, we report a case of sclerosing mediastinitis with bronchial stenosis discovered 1 yr after external radiotherapy for lung cancer. The patient was treated with a Dumont stent and has so far had an uneventful further course for up to 42 months. Bronchial stenosis related to mediastinal fibrosis after radiotherapy has not been reported previously.
The indications and limits of radiotherapy in the treatment of lung cancer are reviewed underlining the importance of different factors: the size of the tumours, the extension but also the treatment parameters (dose conformal, volume and technique). New perspectives are also seen: conformation radiotherapy and studies of changes in fractionation.
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PURPOSE: This study investigated the role of histologic tumor characteristics, in comparison with a normal tissue, and of tumor vascularization on the uptake and retention of colloidal 32P used in infusional brachytherapy of solid cancers. The cytotoxicity of colloidal 32P was also evaluated for two tumors of different radiosensitivity, a melanoma, and a squamous cell carcinoma. METHODS AND MATERIALS: An in vitro analysis of colloidal 32P uptake was carried out on a human melanoma cell line, HBL, a human squamous cell carcinoma, SCC1, and normal fibroblasts, F-NBB. Tumor retention of colloidal 32P was studied in vivo for the HBL and the SCC1 tumors implanted subcutaneously in nude mice. Tumor vascular density was determined by microscopic study of Masson's trichrome slides of HBL and SCC1 tumors of about 1 cm diameter. RESULTS: In vitro studies showed that the time required for maximal cell uptake of colloidal 32P was only 10-20 min for the SCC1 and HBL tumors, while it took at least 60 min for the fibroblasts. After intratumoral injection of macroaggregated albumin (MAA), followed by 50 microCi of colloidal 32P, Bremsstrahlung imaging performed at 6 and 24 h showed that the activity remained in the HBL tumor while some of the radiocolloids leaked from the SCC1 tumor and was trapped in the reticuloendothelial system of the liver. Organ activity counting confirmed this finding: 32P activity was three to four times higher in the HBL than in the SCC1 tumor, whereas the activity in the liver, insignificant in the HBL mice (less than 0.1 microCi/g), was as high as 24 microCi/g in the SCC1 mice. This phenomenon may be explained by the difference in tumor vascular density, estimated for the HBL to be about four times less than that of the SCC1 tumor (5.7 vs. 21.4 blood vessels per mm2 for the HBL and the SCC1 tumors, respectively). CONCLUSION: Intratumoral infusion of colloidal 32P may be a useful complement of radiation therapy in the treatment of nonresectable but accessible solid tumors. Tumor vascularization must be taken into account for a successful vascular blockade by MAA prior to the infusion of colloidal 32P.
PURPOSE: To study the cell kinetics and chromatin modifications occurring in function of the fractionated irradiation administered to the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: The MXT tumor cells were submitted to three fractions of a 4.8 Gy dose delivered at 24-h intervals. MXT tumor cells were collected by means of fine needle aspirations (between 5 and 10 samples were obtained after each irradiation) during treatment and submitted to the computer-assisted microscope analysis of Feulgen-stained specimens. Three groups of parameters has been described: i.e., the geometry of the nucleus, the nuclear DNA content, and the chromatin texture. Furthermore, cell cycle parameters were studied in the aim to know the distribution of the cells within the cell cycle. RESULTS: The mean values relating to geometric parameters (i.e., the nuclear area and its standard deviation) decreased during treatment. Variations in the nuclear DNA content appeared as being cyclical and could be explained in terms of the modifications in the distribution of the cells within the cell cycle. The quantitative analysis of the cell cycle parameters revealed that the percentage of S cells increased regularly after each irradiation. In contrast, the percentage of G2 cells decreased between each irradiation. The parameters describing nuclear texture showed regular variations between each irradiation. These variations consisted in two cycles constituted by a decrease in chromatin condensation, followed by an increase. CONCLUSIONS: The development of the geometric parameters indicates that fractionated radiotherapy leads to the emergence of a more homogeneous population. The effects of the radiotherapy on the distribution of the cells within the cell cycle could be explained through the phenomenon of repopulation and by the high degree of radiosensitivity of the G2 cells (decrease in the percentage of G2 cells). Last, the variations observed at chromatin pattern level could be explained through DNA repair processes.
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Despite the lack of characteristic features, demyelination is the dominant feature of radiation induced late effects observed in cerebral nervous system and spinal cord. Acute, subacute and chronic changes are described in terms of pathological, clinical and radiological observations. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, while imaging changes are observed with lower doses. The most widely observed dose limit for the spinal cord is 45 Gy, in the absence of dose modifying chemotherapy. Tumor progression may be hard to distinguish from radiochemotherapy effects. The potential protective role of hyperfractionation is not yet clearly established. Peripheral nerves late effects, although rare, are described.
Until recently, the liver was classified as a radioresistant organ, although it is in fact highly radiosensitive. The realization that the whole liver could be treated safely only with low doses of radiation led to the conclusion that radiation therapy had an extremely limited role in the treatment of intrahepatic malignancies. A resurgence of interest has been observed with the advent of conformal radiotherapy and the introduction of bone marrow transplantation with total body irradiation. The radiation-induced liver disease, often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites, approximately 2 weeks to 4 months after hepatic irradiation. Immediate tolerance is generally surprisingly good, and the subacute radiation injury is followed by a complete asymptomatic healing, although the late lesions may be associated with signs of chronic radiation hepatitis. Radiation hepatitis must be distinguished from chemoradiation-induced-hepatitis occurring in patients undergoing bone marrow transplantation and total body irradiation. Both syndromes demonstrate the same pathological lesion: veno-occlusive disease. The main treatment for radiation hepatitis is diuretics, although soma advocate steroids for severe cases.
Clinical radiation damage to the kidney are nowadays a rare event. Nevertheless, this organ is very sensitive to radiation and dose exceeding 15 Gy may induce severe and life threatening damage many years after the treatment. Prevention remains the best treatment through a precise localisation of the kidneys before any irradiation of the upper abdomen.
Radiation therapy has been for years the treatment of choice of locally advanced non small cell lung cancer. Improvement due to the combination of radiation and chemotherapy has been shown recently through several randomized trials and a recent meta-analysis. These results may be explained by biological mechanisms, yet uncompletely explored, which are detailed in this review and applied to lung cancer. The optimal combination scheme is not yet defined, even though the concurrent approach is promising, at the expense of an increased toxicity which is the limiting factor of treatment escalation doses. Biological findings and future results of randomized trials will hopefully open new avenues in the therapeutic strategy of this poor prognosis disease.
Radiation therapy of benign diseases represent a wide panel of indications. Some indications are clearly identified as treatment of arteriovenous malformations (AVM), hyperthyroid ophtalmopathy, postoperative heterotopic bone formations or keloid scars. Some indications are under evaluation as complications induced by neo-vessels of age-related macular degeneration or coronary restenosis after angioplasty. Some indications remain controversial with poor evidence of efficiency as treatment of bursitis, tendinitis or Dupuytren's disease. Some indications are now obsolete such as warts, or contra-indicated as treatment of infant and children.