Radiation oncology investigations最新文献

We have investigated whether a hydrophilic photosensitizer, chlorin e6Na (Ce6Na), can sensitize cells to ionizing radiation. When V79-1 cells were pretreated with Ce6Na for 2 hr before receiving a dose of 2-14 Gy of irradiation, the cells became sensitive to X-irradiation. The sensitizing effect of Ce6Na depended on the dose of Ce6Na. The sensitizing effect also depended on the length of the treatment period before X-irradiation up to 4 hr, but not on the length of a treatment period after X-irradiation. Intracellular concentrations of Ce6Na were increased linearly after incubation with Ce6Na for periods of up to 4 h. The dose-modifying factor calculated from the survival curve was 1.25.

The optimal dose and schedule of paclitaxel in combination with irradiation have not been determined yet. The aim of this study was to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single vs. fractionated paclitaxel exposure. A fibroblast cell line (B14) in exponential growth phase was used. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Cytotoxicity of Taxol was examined at concentrations varying from 2 to 50 microM. Single (1 x 0 microM) vs. fractionated (2 microM/day, days 1-5) exposure of Taxol was investigated. The combination of Taxol plus irradiation as single and fractionated treatment was accomplished with 10 microM Taxol on day 1 plus 10 Gy irradiation on day 1 vs. Taxol 2 microM/day, days 1-5, plus irradiation 2 Gy/day, days 1-5. One-, 9-, and 24-hr intervals between end of incubation and irradiation were defined. Control populations demonstrated an average plating efficiency of 93%. Single Taxol exposure showed an average clonogenic survival of 84%. No significant difference between concentrations varying from 2 to 50 microM was observed. Single dose irradiation (1 x 10 Gy) led to clonogenic survival of 3%. Single exposure of Taxol plus single dose irradiation led to clonogenic survival of 4%. Fractionated radiation showed an average clonogenic survival of 41%. Fractionated Taxol treatment led to an average clonogenic survival of 63%. The combination of fractionated Taxol treatment (2 microM/day, days 1-5) plus fractionated irradiation (2 Gy/day, days 1-5) showed an average clonogenic survival of 15%. No significant difference between the chosen intervals was demonstrated. Flow cytometric measurements did not indicate any significant alterations in cell cycle DNA distribution. In conclusion, the data demonstrate a potential beneficial effect by combining fractionated Taxol exposure with fractionated irradiation without evidence for G2/M arrest in DNA analysis.

The objective of this study was to document the utility of computed tomography (CT) and a three-dimensional (3-D) radiotherapy treatment planning system for assessing the development of acute radiation pneumonitis in a canine model. Fourteen dogs were randomly assigned to a nonirradiated control group or one of three radiation dose groups receiving a single fraction of either 12, 15, or 18 Gy delivered to two-thirds of the right hemithorax. CT and survey radiographs were performed in all dogs prior to and at defined intervals for up to 13 weeks following irradiation. All images were subjectively evaluated for development of radiation pneumonitis and CT images were quantitatively analyzed. Radiation pneumonitis was detected earlier with CT images than with radiographs. Quantitatively, functional lung volume and radiation pneumonitis lesion volume on CT images changed over time in all irradiated dogs. However, there was no statistically significant difference between the three radiation dose groups, but a marked difference between irradiated dogs and nonirradiated controls. These data suggest that CT is superior to survey radiography for the evaluation and quantification of acute radiation pneumonitis in this canine model. Quantification of acute radiation pneumonitis suggests future promise for evaluating the efficacy of modifiers to lessen the effects of irradiating normal lung tissue in this canine model.

Discoloring of glass due to ionizing radiation depends on the absorbed dose. The radiation-induced light attenuation in optical fibers may be used as a measure of the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber can be calibrated. A dosimeter based on an optical fiber was developed for applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm, whereas the length depends on the sensitivity required. To demonstrate the applicability, a customized fiber device was used to determine scattered radiation close to the lens of the eye. Measurements were compared with TLDs (LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows good agreement. In contrast to TLD, optical fibers provide immediate dose values, and the readout procedure is much easier. Owing to its small size and diameter, interesting invasive dose measurements are feasible.

A relationship between the rate of regression of lymphomas treated with chemotherapy and long-term outcome has been observed. This study was undertaken to determine if the rate of tumor regression during radiotherapy for mediastinal Hodgkin's disease is a predictor of in-field recurrence. Twenty-nine patients with early-stage Hodgkin's disease treated with radiotherapy alone as part of an NCI randomized trial had both a non-massive mediastinal component of disease and all requisite simulation and port films available for analysis. The histology was nodular sclerosis in all patients. Stage distribution was as follows: IA-1; IIA-17; IIB-8; IIIA1-3. The median age was 27 years and the median radiation dose was 4470 cGy. A mediastinal mass ratio was calculated from each patient's simulation and weekly port films by dividing the width of the mediastinal mass by the intrathoracic diameter at the level of the carina. Histopathologic correlation was also done to quantify the degree of tumor vs. sclerosis in the specimens. Univariate analysis and Cox proportional hazards analysis were used to study the association between several covariates (stage, sex, symptoms, extra-lymphatic disease, initial mediastinal mass ratio, age, dose, percent tumor in the specimen, and cumulative percentage of tumor regression) and time to in-field recurrence, as well as probability of any failure. Univariate analysis indicates that lower dose, higher percent tumor in the specimen, and lower cumulative percent regression are statistically significant predictors for in-field recurrence, as well as for any failure. By Cox regression analysis, cumulative percent regression is the sole factor independently associated with in-field recurrence (two-tailed P=0.04). The percent tumor in the specimen is the only factor similarly identified for time to any failure (two-tailed P=0.02). Histopathologic correlation suggests that patients with early stage mediastinal Hodgkin's disease who demonstrate a high percent tumor in the specimen may be at increased risk of failure. Patients with a low cumulative percent regression during radiotherapy appear to be at an increased risk of in-field recurrence.

Tirapazamine is a hypoxic cell cytotoxin in phase II/III trials. To further understand its mechanism of action in vivo, we examined the effect of tirapazamine on tumor energy metabolism and pH. RIF-1 and SCCVII tumors were grown subcutaneously in the flanks of C3H mice. Tumor energy metabolism, expressed as the ratio of inorganic phosphate to nucleotide triphosphate (Pi/NTP), and intracellular pH (pHi), were measured by 31P magnetic resonance spectroscopy (MRS). In RIF-1 and SCCVII tumors, tirapazamine increased the Pi/NTP ratio by 2.6-fold and 3-fold, respectively, within the first hour after an intraperitoneal dose of 0.3 mmol/kg. A corresponding decrease in pHi from 7.05+/-0.07 to 6.48+/-0.06, and 7.21+/-0.09 to 6.45+/-0.02 in RIF-1 and SCCVII tumors, respectively, was observed. The decrease in tumor 31P bioenergetics and pH was reversible, as exemplified by RIF-1 tumors, which showed a further increase in Pi/NTP ratio of 3.5-fold by 5-8 hr, returning to normal range at 24 hr. Corresponding pHi of RIF-1 tumors was 6.88+/-0.05 at 5-8 hr and 7.16+/-0.05 at 24 hr. We concluded that tirapazamine induces acute changes in tumor energy metabolism and pHi. These findings are relevant to the rational selection and optimal timing of coadministered therapy.

Radiotherapy is administered with the assumption that all patients respond similarly to radiation although radiosensitivity does vary from patient to patient, resulting in different degrees of early and late effects. Because the dose given to a patient is limited by the response of normal tissue in the treatment field, it would be beneficial to determine the sensitivity of this normal tissue prior to therapy. Previous studies to predict radiosensitivity have used surviving fractions after a single dose given in vitro, however, differences in cell survival at this low level of kill are not easy to resolve. In this study, we set out to evaluate the use of alternative dose regimens which may better resolve differences in radiosensitivity. We have examined several radiation protocols for predictive value, including survival after high doses (6 Gy) at both high (112 cGy/min) and low (.882 cGy/min) dose rates and after fractionated doses of 2 Gy (6 fractions). A sensitive human fibroblast line (S11358) cultured from a patient showing severe effects after therapy is compared with a cell line (OMB1) cultured from an apparently normal subject. Differences between these cell lines have been compared with those between two human melanoma cell lines (SKMEL3 and HT144) which have shown resistant and sensitive response to radiation in vitro respectively. In both fibroblast and melanoma cell lines, the difference in the survival of normal and sensitive cells increased with increasing dose regardless of whether irradiation was delivered as low dose rate, high dose rate, or as fractionated doses. We propose that radiation doses which more closely mimic clinical treatment are more suitable than surviving fraction after 2 Gy (SF2) for in vitro evaluation of relative radiosensitivities of cell populations.

Forty-seven patients were treated for carcinoma of the extrahepatic biliary tract between 1962 and 1993: 17 by surgery alone, 20 by surgery and postoperative radiotherapy, and 10 with radiotherapy alone. Initial operations included gross total resection (17 patients), simple cholecystectomy (6 patients), subtotal resection (11 patients), biopsy (3 patients), and percutaneous decompression (10 patients). External-beam radiotherapy (30-60 Gy) was administered to 30 patients: 10 after gross total resection or simple cholecystectomy, 10 after subtotal resection or surgical biopsy, and 10 after percutaneous decompression. Overall survival was 26% at 3 years and 15% at 5 years. The 5-year survival rate was 15% for 17 patients treated by surgery alone and 14% for 30 patients treated with radiotherapy alone or following surgery. After gross total resection, median survival time was 26.1 months for 9 patients treated by surgery alone vs. 43.4 months for 8 patients who received postoperative radiotherapy. After gross total resection or cholecystectomy, 5-year survival rates were 19% for surgery alone and 35% for surgery and postoperative radiotherapy (P=.07). Median survival for 10 patients treated by radiation therapy alone after percutaneous decompression was 6.4 months. Postoperative adjuvant radiotherapy was well tolerated and may improve local-regional control after gross total resection.

To compare the dosimetry achievable with an intensity modulated radiotherapy (IMR) system to that of stereotactic radiosurgery (SRS) for an irregularly shaped moderate size target. A treatment plan was selected from 109 single fraction SRS cases having had multiple non-coplanar arc therapy using a 6 MV linear accelerator fitted with circular tertiary collimators 1.00 to 4.00 cm in diameter at isocenter. The CT scan with delineated regions of interest was then entered into an IMR treatment planning system and optimized dose distributions, using a back projection technique for dynamic multileaf collimator delivery, were generated with a stimulated annealing algorithm. Dose volume histograms (DVH), homogeneity indices (HI), conformity indices (CI), minimum and maximum doses to surrounding highly sensitive intracranial structures, as well as the volume of tissue treated to > 80, 50, and 20% of the prescription dose from the IMR plan were then compared to those from the single isocenter SRS plan used and a hypothetical three isocenter SRS plan. For an irregularly shaped target, the IMR plan produced a HI of 1.08 and CI of 1.50 compared to 1.75 and 4.41, respectively, for the single isocenter SRS plan (SRS1) and 3.33 and 3.43 for the triple isocenter SRS plan (SRS3). The maximum and minimum doses to surrounding critical structures were less with the IMR plan in comparison to both SRS plans. However, the volume of non-target tissue treated to > 80, 50, and 20% of the prescription dose with the IMR plan was 137, 170, and 163%, respectively, of that treated with the SRS1 plan and 85, 100, and 123% of the volume when compared to SRS3 plan. The IMR system provided more conformal target doses than were provided by the single isocenter or three isocenter SRS plans. IMR delivered less dose to critical normal tissues and provided increased homogeneity within the target volume for a moderate size irregularly shaped target, at the cost of a larger penumbra.

Although traditional recommendations for the management of bulky cervical lymphadenopathy (AJCC categories N2-3) with definitive radiotherapy call for postradiotherapy neck dissection regardless of treatment response, recent data suggests that this policy can be modified on the basis of tumor regression rate. In a series of 130 patients with stage III-IV squamous cell carcinoma of the head and neck managed with a concomitant boost-accelerated hyperfractionated radiotherapy schedule, 81 cases had cervical lymphadenopathy at the time of referral. Patients were analyzed with respect to regional control outcomes for those having complete and incomplete clinical responses during the initial 3-month follow-up interval. The general management policy has been close observation of patients demonstrating complete clinical responses to radiation rather than postradiotherapy neck dissection. Failure patterns were examined in the 58 patients classified as complete responders. Failure occurred in the primary site in 16 (28%) of these patients, while isolated neck failure occurred in only 3 (5%). Neck recurrence rates for patients with maximum lymph node size < or = 3 cm vs. > 3 cm were not statistically different at 3-year follow-up (94% vs. 86%). Among the 23 incomplete clinical responders, 18 had incomplete neck responses. Five of these patients underwent salvage neck dissection; 4 remain clinically free of recurrence. The remaining 13 patients who either refused or were not eligible for salvage surgery ultimately succumbed with persistent loco-regional disease. The policy of observation after complete response to the radiotherapy schedule employed here was associated with a very low incidence of isolated neck failures and was safe and appropriate in patients who can be followed reliably. The prognosis for patients who failed to respond in the neck was poor except for those who underwent salvage surgery.