Radiation oncology investigations最新文献

The endothelial cell glycoprotein, thrombomodulin (TM), is an important physiological anticoagulant. TM is downregulated and released from the cell membrane into the circulation by ionizing radiation and during inflammation. The present study measured plasma TM in 17 patients before, during, and after radiation therapy of lung cancer: nine patients developed radiation pneumonitis, whereas eight matched patients did not. Plasma TM did not change significantly in patients who developed radiation pneumonitis. In contrast, patients who did not develop pneumonitis exhibited a moderate, but statistically significant, decrease in plasma TM antigen during the initial 1-2 weeks, with complete normalization towards the end of treatment. Our study suggests that decreased release of TM during the early phase of radiation therapy may be associated with reduced pulmonary toxicity. The use of plasma TM as a marker of pulmonary toxicity needs further study.

We reviewed our institution's experience treating patients with prostate cancer with 3-dimensional conformal radiation therapy (3DCRT) and short-term adjuvant hormonal therapy to determine biochemical no evidence of disease (bNED) and clinical outcome compared with patients treated with 3DCRT alone. Between 4/1/89 and 11/30/94, 558 patients with clinically localized prostate cancer received treatment at Fox Chase Cancer Center (Philadelphia, Pa.); 484 patients were treated with 3DCRT alone (Group I); 74 patients were treated with 3DCRT and hormones (Group II). Five-year actuarial rates of bNED control, distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were calculated for pretreatment PSA, Gleason score, T stage, use of hormones, treatment field size, age, and dose. A matched case/control analysis was performed to further evaluate the effect of hormones on treatment with 3DCRT. Median follow-up was 47 months (range: 2-97 months). The 5-year actuarial rates of bNED control, DMFS, CSS, and OS were 66%, 93%, 98%, and 86%, respectively, for Group I patients and 68%, 93%, 98%, and 89%, respectively, for Group II patients. Multivariate analysis demonstrated that hormone use was an independent predictor of bNED control only. A significant difference in bNED control was observed between Group I and II (43% vs. 71%) using the matched case/control analysis (P = 0.02). A trend towards significance was observed for different rates of DMFS between Group I and II (79% vs. 94%, P = 0.09). Patients with clinically localized prostate cancer with poor prognostic features (pretreatment PSA > or = 10 ng/ml, Gleason score > or = 7, and/or T2c or greater palpation stage) show improved rates of bNED control and a trend towards improved DMFS when treated with 3DCRT and short-term adjuvant hormones compared with 3DCRT alone. Long-term observation will be necessary to see if improvements in bNED control will translate into improvements in overall survival.

Because of promising radiobiological advantages allowing dose escalation and/or reduction of treatment time, hyperfractionated and accelerated-hyperfractionated radiotherapy (hf-rt, ahf-rt) were introduced as part of treatment of glioblastoma multiforme (gbm). In December 1988 we started a prospective study of hf-rt (total dose 78 Gy, two daily fractions of 1.3 Gy, interval between daily fractions 6 hr, treatment time 6 weeks, n = 34 patients). The results were compared with our previous regimen of conventionally fractionated radiotherapy (cf-rt: total dose 60 Gy, single dose 2 Gy, treatment time 6 weeks, n = 32 patients). In June 1990, the protocol was modified in order to reduce treatment time (ahf-rt: total dose 60 Gy, two daily fractions of 1.5 Gy, interval 6 hr, treatment time 4 weeks, n = 92 patients until December 1996). No chemotherapy was given. Entry criteria were: age > or = 17 years, pathological diagnosis of supratentorial gbm, and no previous treatment other than surgery. The ahf-rt group included significantly more patients with previous surgical resection instead of biopsy only. Compared with the cf-rt group, both the hf-rt and the ahf-rt group included significantly more patients with frontal tumor location. We found no significant survival difference between the groups (median survival 7-10 months, 1-year survival rate 19%-29%). Progression-free survival, clinical course, and toxicity were also not significantly different. Karnofsky performance status, age, and corticosteroid dose during radiotherapy were the most important prognostic factors. The results of this trial are in large agreement with most previous publications. It demonstrated no improved survival. However, it showed that treatment time can be reduced by ahf-rt without loss of survival benefit or intolerable toxicity. A short radiotherapy course might be appropriate for many patients with gbm who are not suitable for rather aggressive investigational therapies.

This article discusses recent advances in basic research that alter the view of the pathogenesis of radiation myelopathy and summarizes the available data from developmental neurobiology and preclinical studies on demyelinating diseases. These studies have produced interesting insights into oligodendrocyte development, intercellular signaling pathways, and myelination processes. Current findings suggest that administration of cytokines as platelet-derived growth factor and basic fibroblast growth factor could increase proliferation of oligodendrocyte progenitors, enhance their differentiation, up-regulate synthesis of myelin constituents, and promote myelin regeneration in the adult central nervous system (CNS). Other compounds might also be able to modulate the progression of pathogenic processes that lead to myelopathy. In addition, several possible biological prevention or treatment strategies, for example stimulation of endogenous cellular regeneration and glial cell transplantation, are discussed. Rationally designed animal experiments pursuing such strategies could further elucidate the pathogenesis of radiation-induced CNS damage.

To determine the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy (HDCT) and radiation therapy (RT), failure sites were reviewed in 56 patients. Twenty-one (38%) received involved-field RT (IFRT) before or after HDCT encompassing sites of prior disease. Failure sites were designated as previously involved (old) or uninvolved (new) sites. Seven patients (12%) died in the immediate post-HDCT period, leaving 49 evaluable (median follow-up, 41 months). Twenty-five patients (51%) relapsed (14 HDCT, 11 HDCT + IFRT): seven (28%) in old, eight (32%) in new, and ten (40%) in old and new sites. Six of the seven who relapsed in old sites received HDCT alone, whereas seven of the eight who relapsed in new sites received IFRT. Relapse in old sites was particularly common in patients failing to achieve a complete response. The most common new failure site was nodal, occurring in 11 patients and was primarily (10/11) adjacent to an old site. Although it controls prior disease, IFRT is insufficient in Hodgkin's disease patients undergoing HDCT. Relapse is common in new nodal sites and is primarily adjacent to prior sites. These results suggest that extended-field RT encompassing old and adjacent uninvolved nodal sites may be the optimal treatment volume in these patients.

Between 1964 and 1996, 123 patients were treated for T4 oropharyngeal carcinoma; 93 were treated with radiation therapy alone; 30 were treated with induction chemotherapy and radiation therapy. Patients who received induction chemotherapy and radiation therapy were treated between 1985 and 1996; during this time 39 patients were treated with radiation therapy alone. Five-year local control rates for patients undergoing chemotherapy and radiation therapy, radiation therapy alone (all patients), and radiation therapy alone (patients treated since September 1985) were 63%, 38%, and 48%, respectively. The five-year rates of freedom from distant metastasis were 87%, 73%, and 76%, respectively. The five-year actuarial cause-specific survival rates were 58%, 27%, and 37%, respectively, while the five-year absolute survival rates were 42%, 17%, and 23%, respectively. Improvements in local control and freedom from distant metastasis in those receiving chemotherapy were not statistically significant, while the improvements in cause-specific survival and absolute survival were significant at the P < or = 0.05 level. Induction chemotherapy may improve the cure rate for patients with T4 oropharyngeal carcinoma. Although encouraging, these data are nonrandomized and should be interpreted with caution.

To study the efficacy and safety of relatively low-dosed reactor fission neutron therapy (RENT) at the research reactor of the Technical University Munich, we treated 33 superficial lesions of 20 patients with advanced malignant melanoma by neutron beam alone (n = 22), mixed neutron/electron beam (n = 5), or by neutron beam after incomplete surgery (n = 6). Median tumor volume was 17.0 cm3. Median dose for neutron beam alone was 8.0 Gy and for mixed beam 3.0 Gy n + 45.3 Gy e-. Local tumor response, local control time, survival and treatment related toxicity were followed prospectively over a time period of 52 months. Overall response rate (CR;PR) after neutron beam alone and mixed beam therapy was 64% (CR: 36%) and 100% (CR: 60%), respectively. Observed differences between complete (CR) and incomplete (PR, NC) responding lesions were as follows: median tumor volume: 2.0 vs. 51.5 cm3, local control time: 13.3 vs. 3.7 months, median survival: 19.8 vs. 9.0 months. No severe acute or late sequelae could be observed. In conclusion, low-dosed RENT is an effective and well tolerated palliative treatment of superficial malignant melanoma utilizing the biologic advantage of diminished cellular repair capacity. Because melanoma lesions of small size (< or = 6 cm3) tend to respond completely, neutron beam should be performed at an early stage.

The genetic determinants for most breast cancer cases remain elusive. However, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or ATM, has been determined to be one mechanism of breast carcinogenesis. It has been established that inherited mutations in p53, BRCA1, and BRCA2 significantly contribute to breast cancer risk, although the importance of an inherited ATM mutation is controversial. Sporadic mutations in p53 are also common in breast cancer cells. The precise deficiencies that result from these genetic mutations have yet to be fully described. Although the functions of these genes are different, they are all involved in the maintenance of genomic stability after DNA damage. Mutations that impair the function of these four genes may adversely affect the manner in which DNA damage is processed. It is likely that the risk of breast cancer development is increased through this mechanism. In this article, we review the relevancy of p53, BRCA1, BRCA2, and ATM mutations to breast cancer development, and review the in vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair.

Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment.

This study was designed to evaluate the combination of docetaxel (Taxotere) and carboplatin for radiopotentiation in vitro. H460 human lung carcinoma cells were treated with docetaxel (or paclitaxel) for 1 h and rinsed. After 24 h, the cells were treated with carboplatin for 1 h, irradiated, and colony forming ability was assesed. Using various doses of docetaxel with 100 microM carboplatin, the dose enhancement ratio (D.E.R.) for drugs only was 1.26. When 25 nM docetaxel was used with various doses of radiation, the radiation D.E.R. was 1.41. With all three agents combined, and after normalization for combined drug effects, the radiation D.E.R. was 1.55. Similar values were obtained using paclitaxel with these agents. Significant redistribution of cells into the radiosensitive G2/M phase was observed using a dose of paclitaxel (750 nM), which also caused radiation enhancement. However, an equally cytotoxic dose of docetaxel (25 nM) did not result in any cell cycle redistribution; this phenomenon was only observed at higher doses. This study shows that the combination of docetaxel and carboplatin enhance the effects of radiation in vitro more effectively than either drug seperately. In addition, our data show that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in H460 cells.