Radiation oncology investigations最新文献

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.

Esophagitis is a major toxicity of radiation therapy for nonsmall-cell lung cancer. Intraesophageal injection of manganese superoxide dismutase (MnSOD) plasmid/liposome complexes (1 mg of the pRK5-MnSOD plasmid containing the human MnSOD transgene in a 0.15 ml volume of lipofectin) before irradiation was carried out to attempt to prevent irradiation esophagitis. In control noninjected male C3H/HeNsd mice, esophagitis was induced by single fraction 3,500 cGy irradiation. Histopathology at 4 days revealed vacuole formation in squamous lining cells, separation of the squamous layer from the underlying muscle layer, ulceration at 7 days, and dehydration and death by 30 days. MnSOD plasmid/liposome complex-injected mice showed transcription of the human MnSOD transgene message in esophageal squamous lining cells by nested reverse transcriptase-polymerase chain reaction (RT-PCR) increased MnSOD biochemical activity 24 h after injection, decreased vacuole formation at day 4 (P < 0.001) after 3,500 cGy thoracic irradiation, and improved survival (P = 0.0009). In contrast, groups of mice receiving LacZ (bacterial beta-galactosidase gene) plasmid/liposome complexes or liposomes containing no DNA before 3,500 cGy irradiation showed an unaltered irradiation histopathology and decreased survival. Mice receiving intraesophageal MnSOD plasmid/liposomes followed 8 h later by human equivalent doses of Taxol (1.4 mg/kg) and carboplatin (2.5 mg/kg), then 15 h later 3,300 cGy irradiation, showed increased survival, compared with irradiated control or LacZ plasmid/liposome groups. Thus, overexpression of the human MnSOD transgene in the esophagus can prevent irradiation-induced esophagitis in the mouse model.

The amino acid analog azetidine-2-carboxylic acid (azetidine) is a potent sensitizer to both hyperthermia and ionizing radiation. Incubation of H35 hepatoma cells with 2.5 mM azetidine before or after treatments with X-rays causes a time- and sequence-dependent enhancement of cell killing. Exposure of cells to 1-1.5 mM azetidine for 96 h in combination with repeated doses of 3 Gy X-rays at 24 h intervals causes an enhanced reduction of the surviving cell population due to both radiosensitization and an additional growth inhibition. Azetidine does not prevent the induction of thermotolerance after a heat shock. This thermotolerance proportionally reduces thermal radiosensitization but does not seem to affect azetidine radiosensitization. It is suggested that thermal radiosensitization and azetidine radiosensitization operate by different mechanisms.

The linear quadratic model predicts that the normal tissue biologically effective dose (BED) will be lower with palladium-103 (Pd-103) vs. iodine-125 (I-125) for the currently prescribed minimum tumor doses (MTD) used for I-125 (160 Gy) and Pd-103 (115 Gy) prostate cancer brachytherapy. The predicted BEDs for I-125 and Pd-103 suggest that the long-term complication rates should be lower with Pd-103 vs. I-125 in clinical practice. A review of 123 early stage T1c and T2 prostate cancer patients implanted at Yale University with I-125 (82 patients) or Pd-103 (41 patients) reveals a significantly lower overall complication rate with Pd-103 (0%) vs. I-125 (13%). Most important, the grade III-IV complication rate for Pd-103 was 0% vs. 6% for I-125. The 3-year actuarial probability of remaining free of a long-term complication was 100% for Pd-103 vs. 82% for I-125 (P<0.01). A review of the literature for 992 patients implanted with I-125 vs. 540 patients implanted with Pd-103 shows a consistently higher complication rate for I-125 vs. Pd-103. Assuming that the MTD for Pd-103 may be increased to produce an equivalent late-reacting normal tissue BED to that for I-125, then the radiobiology model predicts the log10 cell kill for Pd-103 implant will be greater than that of an I-125 implant for all tumor doubling times (high-grade tumors and low-grade tumors). The implications of these findings are discussed in terms of future research directions for prostate implants.

The purpose of the study was to determine which clinical parameters might predict individual prostate volume changes from prostate brachytherapy. Fifty consecutive, unselected patients treated at the University of Washington by I-125 or Pd-103 implantation for prostatic carcinoma in 1998 were analyzed. The prostate contours on preimplant transrectal ultrasound (TRUS) images were digitized and the prostate volumes calculated. Postimplant axial CT images of the prostate was obtained at 0.5 cm intervals with patients in the supine position the morning after the implant. The postimplant prostate volume increased by an average factor of 1.7 (+/-0.34) compared with the preimplant volume, the size increase being primarily in the anterior-posterior dimension. The absolute volume change was similar in patients with small vs. large preimplant prostate volume (r = -0.39), but the proportional change was less in patients with a larger prostate volume (r = -0.71). Because patients with a small preimplant prostate had proportionately greater volume increase, their postimplant target coverage was generally less. No single parameter, including preimplant prostate volume, preimplant hormonal deprivation, or supplemental external beam radiation therapy (EBRT) can accurately predict the degree of swelling. The precise significance of and practical solution to implant-related prostate volume changes remains to be determined.

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.

Cervical cancer was treated with a combination of external beam and intracavitary radiation during a 10-year period at Wayne State University. Data were collected for 216 patients treated radically with external beam radiation (EBRT) and low-dose-rate brachytherapy for cervical cancer between 1980 and 1991 at Wayne State University. Patient distribution by stage was IB, 20.8%; IIA, 7.4%; IIB, 26.9%; IIIA, 1.8%; IIIB, 40.7%; and IVA, 2.3 %. Survival curves were constructed using Kaplan-Meier methods and differences between groups were tested for significance using the log-rank test. Multivariate analysis was done using the Cox proportional hazards model. With a median follow-up of 114 months, actuarial disease-free survival for all patients was 60% at 5 years and 55% at 10 years. Actuarial 5-year survival for Stage IB was 79%; for Stage II, 59%; and for Stage III, 53%. There were 14/216 (6%) of patients with severe late complications. On univariate analysis, race was found to be statistically significant, with Caucasian patients having better survival than African American (P = 0.03). The survival for patients treated in shorter overall times was significantly higher (P<0.001), especially with treatment completion in under 58 days. The stepwise Cox multivariate analysis provided the following significant results: race (African American vs. Caucasian; P = 0.04, RR = 1.6), Stage (II vs. I, P = 0.004, RR = 2.6), Stage (III vs. I; P = 0.004, RR = 2.5), and overall treatment time (P = 0.006, RR = 1.62). Rates of local control, survival, and complications among women treated with combined external beam and intracavitary radiation for cervix cancer were similar to those of prior retrospective studies.

Accurate knowledge of the distribution and amount of contamination electrons arising from the gantry head at the surface and in the first few centimeters of tissue is essential for the clinical practice of radiation oncology. These electrons tend to increase the surface dose and deteriorate the buildup in the radiation field compared with a pure photon field. In this study, the relative quantity and reduction of contamination electrons in a therapeutic radiation photon beam (15 MV) was investigated. The contamination electrons can be separated out by a special device. This device, consisting of a double-focus electric field (8 x 10(5) V/m) made by a large number of strings 2 x 10(-4) m in diameter, removes contamination electrons and positrons without affecting the photon beam. It is located under the tray holder. In clinical practice, the device can decrease the relative surface charge and relative surface dose due to contamination electrons in the photon beam used in radiation therapy.

A simple five-seed assay method was proposed and investigated. A commercial well ion chamber system with an NIST-traceable single-seed calibration constant was used for the single-seed assays. A batch seed holder was used for batch assays. For the five-seed assays, a second single-seed holder was modified such that all five seeds were loaded in a central region of the well ion chamber. Compared with the same seed in the standard single-seed holder, the relative chamber responses for the five seed positions were 0.993, 0.993, 1.000, 1.001, and 0.977, respectively, indicating little or no position-dependent chamber response and no self-attenuation among seeds. Subsequent comparison of assays with the single-seed and five-seed methods indicated only 0.4% difference in charge collection. The five-seed calibration constant was therefore taken to be the same as the single-seed calibration constant. The reproducibility of the five-seed assay method was found to be better than 0.8%. When a dummy seed replaced an active seed, a nearly 20% reduction in charge was found, indicating that the proposed five-seed assay method can detect a dead seed. Clinical comparison of all three assay methods showed that they produced qualitatively the same assay results when the batch assay method was performed with extra care. Compared with the single-seed assay method, the five-seed method is equally simple, rigid, and reproducible, but it demands much less assay time. Compared with the batch assay method, the five-seed method is much more reproducible and reliable because of its rigid assay geometry; it only demands a moderate amount of assay time and can detect dead seeds. The American Association of Physicists in Medicine Task Group 40 (AAPM TG40) states that, for brachytherapy, ideally every (i.e., 100%) loose seed should be calibrated. For procedures involving large number of loose seeds, it then recommends that 10% of seeds be calibrated. The proposed five-seed assay is very simple to implement. It will facilitate the compliance of the "10%" recommendation from the AAPM TG40; it will make the "ideally 100%" statement from AAPM TG40 a more realistic and practical QA procedure in seed assaying.