Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

Postoperative single-dose interstitial high-dose-rate brachytherapy in therapy-resistant keloids.

PURPOSE: Patients with keloids complain of the cosmetic aspect, pain, and pruritus. Many different therapies are being used for keloids. The aim of this study was to evaluate the recurrence rate and outcome after resection followed by a single-dose brachytherapy. METHODS AND MATERIALS: Patients treated by resection of the keloid plus a single dose of 13 Gy high-dose-rate brachytherapy were evaluated at least 1 year after treatment. Clinical response and cosmesis were assessed by a plastic surgeon and by the patients using the Patient and Observer Scar Assessment Scale. RESULTS: Only 24 of the 61 invited patients responded to participate with the study; 29 keloids were evaluated. The recurrence rate was 24.1% after a median followup of 53 months (19-95 months). Patients scored on average 24.3 for their total Patient and Observer Scar Assessment Scale score (range 6-52), whereas the observer scored on average 14.6 (range 6-42). CONCLUSIONS: This treatment has a higher recurrence rate than that reported in most other studies. This may be explained by differences in recurrence definition, differences in followup time among studies, and selection bias because of not contributing to the study. The cosmetic outcome for evaluated patients is relatively good. This treatment policy has the advantage that patients are treated in a single day.

Time course of enhanced activity of deoxycytidine kinase and thymidine kinase 1 and 2 in cultured human squamous lung carcinoma cells, SW-1573, induced by gamma-irradiation.

Single high dose rate irradiation of 4 Gy in SW-1573 cells, derived from non-small cell lung cancer, led to increased activities of deoxycytidine kinase (dCK) and thymidine kinase 1 and 2 (TK1 and 2). The activity of dCK increased by approximately 30% between 1 and 5 h after irradiation, after which the activity returned to the level of control cells by 8 h after irradiation. TK1 activity also increased by 30-50% between 1 and 6 h after irradiation. The decline to normal levels of dCK concurred with a further increase in the activity of TK1, 8 h after irradiation. TK2 activity was below control levels during the first 4 h after irradiation but rose 3-fold at 8 and 16 h after treatment. The activities of TK1 and TK2 had returned to approximate control levels 24 h after irradiation. The observation that mitochondrial TK2 activity increased to a very high level after irradiation may indicate that the activity of this enzyme is not only important for the damage to mitochondrial DNA, the increased activity may also be instrumental for repair of damage to nuclear DNA. We presume that the increase in activity of TK1 after irradiation is limited to cells in S-phase. Recruitment of cells into S-phase, to replace cells killed by irradiation, is probably too slow to offer an explanation for the enhanced activity of TK1 8 h after irradiation. The increase in activity of both dCK, and TK1 and 2 might be involved in an adaptive response of the cells to radiation by facilitation of DNA repair. The expression of protein kinase C (PKC) decreased during the first 5 h after irradiation. At 5 h after irradiation the level of expression had decreased by >50%. The decrease in PKC expression is concurrent with the increase in dCK activity. This suggests a role of PKC in the signal transduction from DNA damage to the increase in activity of enzymes instrumental in DNA repair.

Quantification of image distortions on the Utrecht interstitial CT/MR brachytherapy applicator at 3T MRI.

PURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method. MATERIALS AND METHODS: An MR-compatible phantom suspending the applicator in water was built and imaged on a Philips Ingenia 3T MRI scanner. A map of the magnetic field (B0) was calculated from multiecho images and used to quantify the field inhomogeneity. The expected displacements of the applicator could be quantified using the measured field inhomogeneity and sequence bandwidth. Additionally, two scans were acquired using opposing readout gradients. These scans were rigidly matched and their displacement was compared with the expected displacements from the B0 map. These same methods were applied in 4 patients. By rigid matching of the scans acquired with opposing readout direction the applicator displacement due to image distortion from B0 inhomogeneity as well as patient movement and organ deformation was determined. RESULTS: According to the B0 map, the displacement on the intrauterine device of the plastic brachytherapy applicator was <0.4 mm for both the phantom and patients. Displacements obtained by the opposing readout method were ≤0.8 mm for each patient with a mean ± SD over the patients of 0.3 ± 0.1 mm. CONCLUSION: The results of our study indicate that the B0 method agrees with the opposing readout method. Displacements caused by magnetic field inhomogeneity on 3T MRI were small compared with displacements due to patient movement and organ deformation.

Effects of hyperthermia applied to previously irradiated cervical spinal cord in the rat.

Rat cervical spinal cord was X-ray irradiated at doses of 15, 18, 20 and 26 Gy. Ninety days later, approximately the same part of the spinal cord was heated at 42.3 +/- 0.4 degrees C for 50, 60, 75 or 90 min by means of a 434 MHz microwave applicator. After treatment, animals were observed over a period of 18 months for expression of neurological complications. These complications could either be the result of the heat or of the radiation treatment. The time course showed three distinct peaks in the incidence of neurological symptoms. The first peak was due to the acute response to hyperthermia. The ED50 value for neurological complications one day after treatment at 42.3 +/- 0.4 degrees C was 74 +/- 2 min. Previous X-ray irradiation of the spinal cord with 18, 20 and 26 Gy reduced the ED50 to 57 +/- 7, 65 +/- 4 and 55 +/- 5 min (12-26% of control), respectively. Recovery from heat-induced neurological complications was diminished in previously irradiated animals. The second peak (150-300 days after X-rays) concerned the expression of "early delayed" radiation damage. Hyperthermia given 90 days after irradiation did not influence either the percentage of animals with paralysis or the latent period. Neurological symptoms developing after day 300 were due to the "late delayed" radiation response. No significant difference was observed in the data on paralysis induced by radiation alone or radiation followed by heat. The late radiation-induced minor neurological symptoms were, however, influenced by retreatment with heat.

The development of PdNi thermoseeds for interstitial hyperthermia.

Magnetic induction heating of thermoseed implants can be used to produce highly localized hyperthermia in deep-seated tumors. Automatic temperature control throughout the tumor can be achieved by the self-regulating character of ferromagnetic seeds, which corrects for local variations in heat loss due to blood perfusion. An increased sharpness of the ferromagnetic transition at the Curie temperature, Tc, improves the performance of self-regulating control. This was realized for palladium-nickel alloys by a "cold working" procedure preceded and followed by annealing. Palladium-nickel seeds with a predetermined Tc were produced, showing a sharp decrease at Tc of the magnetic susceptibility and the heat production.

Dose to fingertips of staff preparing stranded iodine-125 seeds for permanent prostate implants.

The aim of this study is to measure radiation dose to the fingertips of occupationally exposed workers handling stranded iodine-125 seeds during prostate implants. The doses were measured by thermoluminescence dosimetry at the nail of the index finger of both hands in three hospitals in the Netherlands. In all hospitals, measurements were carried out during the preparation of stranded IBt seeds, type Intersource(®) 1251L. The fingertip doses per procedure (mean ± SD) to the fingertip for workers from the three hospitals were estimated to be 0.29 ± 0.15 mSv (n = 6), <0.03 ± <0.02 mSv (n = 8) and 0.31 ± 0.16 mSv (n=16), respectively. The lower doses found for the hospital 2 workers are presumably related to the heavier shielding and longer utensils used in that hospital. Even in the case of hundreds of implant procedures per year, dose to the fingertips for occupationally exposed workers preparing stranded seeds is expected to be well below the annual limit for extremities of 500 mSv.

Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma.

PURPOSE: To perform an analysis of the results obtained with radiotherapy in patients with either resectable or unresectable cholangiocarcinoma of the proximal bile ducts. Emphasis will be paid to analyse the role of radiotherapy, particularly brachytherapy. PATIENTS AND METHODS: Between 1985 and 1997, 109 patients received radiotherapy. In 71 patients (group I) tumor resection was combined with postoperative irradiation in 52 patients and pre- plus post-operative irradiation in 19 patients. Among this group, 41 patients had a boost of 10 Gy to the biliodigestive anastomosis using intraluminal brachytherapy. Median total dose was between 50-55 Gy. The other 38 patients (group II) had an unresectable tumor at laparotomy (16 patients) or were considered primary unresectable because locoregional tumor extension (22 patients). Brachytherapy boost through a nasobiliary approach was given to 19 patients (22-25 Gy). The median total dose varied between 60 to 68 Gy. Mean follow-up was 25 +/- 23 months. RESULTS: In group I, the survival rates at 1, 3, and 5 year were 84%, 37%, and 24%, respectively. Median survival was 24 months. Sixteen patients did live longer than 4 years. Analysis of prognostic factors among resected patients showed the tumor differentiation grade, microscopically involved margins other than the upper (hepatic) and lower (choledocus) resection parameters analysed, only the total dose had influence on margins, and elevated alkaline phosphatase as factors which significantly influence survival. From the different radiotherapy prognosis, patients receiving a total dose above 55 Gy had a shorter survival. It is important to note that patients receiving brachytherapy boost did not have a better survival than patients treated with external beam irradiation alone. Preoperative radiotherapy did not have impact on survival but recurrences in the surgical scars were not observed as compared to 15% recurrences if preoperative radiotherapy was not given. In group II the median survival was 10.4 months. Survival rates at 1 and 2 year were 43% and 10%, respectively. The only significant prognostic factor found was if unresectability was defined primarily or during laparotomy. As it was the case in group I, brachytherapy boost did not have influence on prognosis as compared to external beam irradiation alone. Observed late complications consisted of duodenal stenosis, upper digestive tract bleeding and cholangitis. Probably these complications were not only attributable to radiotherapy, as tumor relapse was also present in the majority of the cases. CONCLUSIONS: The role of radiotherapy either as adjuvant or as primary treatment remains to be demonstrated in prospective randomised studies. From our results, it seems that high radiation doses could be dangerous and could detriment prognosis. Brachytherapy boost was not superior to treatment with external beam irradiation alone.

Analysis of biopsy findings and implant quality following ultrasonically-guided 125I implantation for localised prostatic carcinoma.

Transperineal ultrasound-guided 125I implantation was undertaken in 52 patients with localised prostate cancer. After implantation, ultrasound-guided biopsies were taken from the previous malignant areas every 6 months in all patients. The percentage of negative biopsies increased from 22% at 6 months to 50% at 48 months. Implant quality was analysed in 37 patients. The difference between isodose levels encompassing the prostate and the aimed levels of 160 Gy was taken as a measure of implant quality. A good quality implant (< 10% underdosage) was found in 43% of patients, a moderate quality (10-25% underdosage) in 35%, and a poor quality implant (> 25% underdosage) in 22%. A statistically significant correlation was found between the quality of the implant and resulting negative biopsy at the original tumour site. Determination of prostate specific antigen (PSA) was not possible from the beginning of the study but an analysis with biopsy findings, implant quality and prostate volume reduction during follow-up has been performed since 1989. A significant correlation was observed between implant quality and serum PSA, and also between volume reduction and serum PSA.

Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme.

BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM.