Radiation oncology investigations最新文献

In an attempt to verify the relative efficacy of early concurrent vs. sequential timing of thoracic radiotherapy (TRT) and platinum/etoposide chemotherapy, 48 patients with limited-stage small cell lung cancer treated with either early-concurrent (29 patients) or sequential (19 patients) TRT and platinum/etoposide chemotherapy were evaluated. Disease-specific prognostic variables and the role of prophylactic cranial irradiation (PCI) were also analyzed. Thirty-four patients (71%) received TRT to a dose of 45 Gy in 25 fractions (range, 30-55 Gy). Most patients (75%) received 4-6 cycles of chemotherapy. Twenty-one of 27 patients achieving a complete response after completion of TRT and chemotherapy received PCI. Median follow-up was 29.3 months (range, 12-98 months). Variables of potential prognostic significance were evaluated by both univariate and multivariate analysis. The absolute and relapse-free survival rates for all patients were 42% and 35% at 2 years and 32% and 31% at 5 years, respectively. Thirty-six sites of failure were observed in 27 patients. Thoracic recurrence occurred in nine patients, and the central nervous system (CNS) was the most common site of distant failure (15 patients). Multivariate analysis demonstrated that (a) early concurrent TRT and chemotherapy vs. chemotherapy followed by sequential TRT and (b) disease volume [less than or greater than one-third of the thoracic width] were significantly predictive for survival (P=0.036 and P=0.05, respectively). Rates of control of thoracic disease were 79% for patients with a disease volume less than one-third of the thoracic width vs. 36% for disease volumes greater than one-third of the thoracic width (P=0.0009). Early concurrent TRT and chemotherapy resulted in a significantly lower incidence of distant metastasis (26% for concurrent vs. 63% for sequential; P=0.008). In patients who received PCI, the CNS control rate was 86% vs. 56% in patients not treated with PCI. Our findings suggest that (a) treatment with early concurrent TRT and platinum/etoposide chemotherapy may improve survival when compared with sequential treatment and (b) PCI for patients with complete systemic responses is effective in preventing CNS recurrence. We also conclude that thoracic disease volume is a significant prognostic factor for both local control and overall survival.

Proliferating cells in tumors may be of considerable relevance in cancer therapy. Not only do such cells dictate the rate of tumor progression, but evidence exists that they may also play an important role in the diagnosis and prognosis of tumor regrowth. Consequently, the identification of this subset of cells in the overall neoplastic cell population is of considerable importance. The aim of the present investigations was to compare four flow cytometric methodologies commonly used to study cell proliferation. These included nuclear antigen Ki67 detection, acridine orange (AO) and bromodeoxyuridine (BrdUrd) staining, and percent S-phase determinations. Three human tumor cell lines (HEp3, A549, H226) were examined in various stages of growth. Further, a direct comparison was made of the proliferation activities of HEp3 cells grown in culture or as xenografts in nude mice. The results showed that of the techniques investigated, detection of the nuclear antigen Ki67 may be most useful for marking proliferating tumor cells and determining tumor growth fractions.

Primary spinal cord tumors are rare, and treatment recommendations are therefore difficult. We reviewed a 22-year experience of postoperative radiotherapy for spinal cord tumors to elucidate prognostic factors and recommendations. Twenty-two patients with spinal cord tumors were treated from 1969-1991. Ten patients had ependymomas, of which two were high grade. Twelve had astrocytomas, of which 4 were high grade. Karnofsky status, age, extent of resection, tumor histology, grade, and radiation dose were evaluated, as well as degree of clinical improvement after treatment based on change in Karnofsky status. Ependymomas achieved 100% local control with postoperative radiotherapy. Grade and dose were of indeterminate significance because of these excellent results. High-grade astrocytomas all recurred and caused death. Disease recurred in 1 of 8 patients with low-grade astrocytic or mixed astrocytic tumors. The only prognostic variables of significance were histology, grade, and change in Karnofsky status after treatment. Radiation of primary spinal cord tumors is rare. In nearly all cases, local fields may be used. Improvement in Karnofsky status after radiotherapy may predict better survival. Treatment recommendations for these rare tumors are discussed.

Experiments have been performed to elucidate whether the dose-response relationship for radiation transformation is likely to be due to the fraction of cells altered by the radiation exposure or to the degree of initiation in individual cells. Radiation doses of 0.25, 1, 4, and 6 Gy were utilized in experiments involving approximately 1 or 300 surviving irradiated cells per dish as the initial cell densities. The yield of transformants was approximately the same for each dose of radiation whether 1 or 300 viable cells per dish was utilized as the initial cell density in these studies. A dose-response relationship could be observed for radiation-induced transformation when single irradiated cells were assayed for their ability to give rise to malignantly transformed cells, suggesting that radiation is capable of altering the degree of initiation in individual cells. These results suggest that the dose-response relationship for radiation-induced transformation is due to the degree of initiation in irradiated cells.

The objective of the work reviewed herein was to evaluate whether a cancerization field-consisting of cells with genetic alterations can be detected within normal-appearing bronchial epithelium. By using fluorescence in situ hybridization (FISH) for trisomy 7, cancerization fields were detected in the majority of cancer patients and also in significant percentages of cancer-free tobacco smokers and former uranium miners. These results suggest that molecular analyses may enhance the power of detecting premalignant changes in bronchial epithelium and may ultimately lead to identifying persons at greatest risk for developing lung cancer.

The aim of this study was to assess changes in prostate volumes and organ movement during a course of external beam irradiation using serial computerized tomographic (CT) scans and three-dimensional treatment planning software. Ten consenting prostate cancer patients underwent repeat CT scans at biweekly intervals during the course of external beam irradiation. The spacing of 5 mm was used because this spacing mimics our clinical treatment approach. Prostate locations were determined by merging CT images using bony anatomy and comparing the differences in the prostate volumes, the edges (anterior, posterior, superior, inferior, and lateral) and centers of the prostate (EoP and CoP, respectively). Compared to the 10 initial treatment planning CT scans, the prostate volume determined by the repeat CT scans tended to be smaller (approximately 14%, P < 0.001). The prostate volumes determined by repeat CT scans tended to be stable with a mean volume of 86% (S.D. = 18%) of the initial CT. When assessed by changes in the EoP, superior movements appeared to be the most common source for concern for adequate coverage of the prostate, while inferior movement was not seen. When assessed by changes in CoP, movement of > or = 3 mm was noted in 47% of the studies in the superior direction, with the average displacement being approximately 2.0 mm. In this study, the prostate volume tended to be smaller 2 weeks after the start of radiotherapy. Moreover, the prostate volumes defined by the serial CT scans were less reproducible than expected. Superior displacement of the prostate is the most common and significant type of displacement, while inferior movement is least frequent when patients are simulated with their rectums empty. Because of the magnitude of daily setup errors, organ movement, and problems with reproducibility in target definition, additional field edge reductions do not appear to be warranted during the delivery of three-dimensional conformal radiotherapy. Efforts should be directed at improving our ability to reduce organ movement and accurately targeting the prostate.

Seventy-one histologically malignant brain tumors, 52 histologically benign brain tumors, and 14 cerebral metastases were characterized according to DNA content and proliferative capacity. DNA ploidy, DNA index (DI), S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd) labelling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were assessed by flow cytometry (FCM). In histologically benign tumors, a high percentage of DNA diploid tumors and a low proliferative capacity in DNA diploid tumors were found. Histologically malignant tumors and cerebral metastases were both found to be characterized by a low percentage of DNA diploid tumors and a high proliferative capacity in DNA diploid tumors. The proliferative capacity of DNA aneuploid benign tumors and that of DNA aneuploid malignant tumors, however, appeared not to differ significantly. The number of DNA aneuploid tumors was small. Duration of S-phase was short (range 3.9-4.7 hr) and appeared not to differ between the three groups. From this, the observed differences in Tpot values should be accredited mainly to differences in LI. High-grade as well as low-grade gliomas both appeared to be characterized by malignant (FCM) features, i.e., 1) a high percentage DNA aneuploidy, 2) a high mean DI (for DI > 1), and 3) a high proliferative capacity.

A technique is described for simulating intracranial radiation fields. The method involves the projection of images from magnetic resonance (MR) scans to orthogonal simulation radiographs. This approach often can supplement and occasionally obviate the need for computerized tomographic (CT) assisted treatment simulation for co-planar beam arrangements in brain irradiation. Because magnetic resonance imaging can be performed in virtually any plane and is routinely carried out in sagittal and coronal planes, transferring tumor volumes to orthogonal simulation films using this technique can be done simply and accurately. The method employs an inexpensive photographic enlarger to superimpose sagittal MR scans on the lateral skull simulation films. Tumor volumes along with other structures of interest are treated onto the film and appropriate fields and blocks are contoured. The technique is performed easily in conjunction with routine simulation sessions, provided that the appropriate MR images are available. It is most suitable for planning treatment of tumors located at midline (e.g., medulloblastomas, craniopharyngiomas, brainstem gliomas, germinomas, etc.). The technique has also been used to verify the accuracy of CT-assisted treatment planning. With relatively minor modifications, eccentric tumors also can be accurately planned, and although we have restricted our description to brain tumours, the technique may be extrapolated to tumors in other sites.

The emergence of tumour cells resistant to chemotherapeutic treatment is a major confounding factor in anticancer treatment. Many chemotherapeutic drugs are DNA damaging agents. Resistance to DNA damage can be acquired via a plethora of different mechanisms, including, surprisingly, loss of DNA mismatch repair activity. The DNA mismatch repair system acts after DNA replication and corrects non-Watson-Crick base pairs and other replication errors. Human cells lacking mismatch repair activity have high spontaneous mutation rates. Frequent frameshift mutations in repetitive DNA sequences are characteristically associated with the defect. This hypermutability at repetitive sequences is termed microsatellite instability. DNA mismatch repair defects underlie a predisposition to cancer and are associated with a significant fraction of apparently sporadic cancer cases. In contrast to many other neoplasms, gross genetic aberrations are rare in cells from tumours with microsatellite instability. In these mismatch repair-defective tumours, certain genes that would normally hinder tumour development are frequently found to be inactivated by frameshift mutations in repetitive DNA tracts within their coding sequences. This implies that the small-scale genome alterations characteristic of mismatch repair defects can act as a driving force in tumour development.