Pulse frequency in pulsed brachytherapy based on tissue repair kinetics.

PURPOSE: Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics. METHOD: Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h. RESULTS: The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant. CONCLUSION: Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.

Neurological observations after local irradiation and hyperthermia of rat lumbosacral spinal cord.

PURPOSE: Investigation of the effects of hyperthermia on the radiation response of rat lumbosacral spinal cord with respect to: (a) incidence of paralysis, (b) latency, (c) histopathology, and (d) tumor induction. METHODS AND MATERIALS: Rat lumbosacral spinal cord with the cauda equina was single-dose irradiated with 15 to 32 Gy of x-rays. Hyperthermia for 30 min at a spinal cord temperature of 41.1, 42.3, and 42.6 +/- 0.4 degrees C was applied 5 to 10 min after irradiation by means of a 434 MHz microwave applicator. Animals were observed for 21 months while recording myelopathy and development of tumors. RESULTS: The latent period for hind leg paralysis decreased with increasing radiation dose from 359 +/- 31 days (n = 9) after 20 Gy to 200 +/- 4 days (n = 5) after 32 Gy. Hyperthermia enhanced the radiation response of the lumbosacral spinal cord as evidenced by shortening of the latent period for paralysis and a decrease in the biological effective dose. After 20 Gy followed by 30 min 41.1 degrees C, latency was diminished to 214 +/- 16 days (n = 7, p < 0.001 vs. 20 Gy alone). The ED50 was 21.1 Gy, which was diminished to values between 16 and 17 Gy if radiation was followed by hyperthermia, giving a thermal enhancement ratio between 1.24 and 1.32. Histopathological examination of the spinal cord after combined treatment of x-rays and hyperthermia showed necrosis of nerve roots. Irradiation with 16, 20, 24, and 28 Gy (n = 77) alone led to tumor induction in 17 +/- 8% of the animals (pooled data). If followed by hyperthermia (n = 96), it was increased to 33 +/- 12% (p < 0.01). Most tumors induced by radiation and hyperthermia were sarcomas. CONCLUSION: First, the radiation response of rat lumbosacral spinal cord was enhanced by heat. Second, latency for paralysis was shortened in the lower dose range. Third, no difference in pathology between x-rays alone or in combination with hyperthermia. Fourth, hyperthermia did increase radiation carcinogenesis.

Office hours pulsed brachytherapy boost in breast cancer.

BACKGROUND AND PURPOSE: Radiobiological studies suggest equivalent biological effects between continuous low dose rate brachytherapy (CLDR) and pulsed brachytherapy (PB) when pulses are applied without interruption every hour. However, radiation protection and institute-specific demands requested the design of a practical PB protocol substituting the CLDR boost in breast cancer patients. An office hours scheme was designed, considering the CLDR dose rate, the overall treatment time, pulse frequency and tissue repair characteristics. Radiobiological details are presented as well as the logistics and technical feasibility of the scheme after treatment of the first 100 patients. MATERIALS AND METHODS: Biologically effective doses (BEDs) were calculated according to the linear quadratic model for incomplete repair. Radiobiological parameters included an alpha/beta value of 3 Gy for normal tissue late effects and 10 Gy for early normal tissue or tumour effects. Tissue repair half-time ranged from 0.1 to 6 h. The reference CLDR dose rate of 0.80 Gy/h was obtained retrospectively from analysis of patients' data. The treatment procedure was evaluated with regard to variations in implant characteristics after treatment of 100 patients. RESULTS: A PB protocol was designed consisting of two treatment blocks separated by a night break. Dose delivery in PB was 20 Gy in two 10 Gy blocks and, for application of the 15 Gy boost, one 10 Gy block plus one 5 Gy block. The dose per pulse was 1.67 Gy, applied with a period time of approximately 1.5 h. An inter-patient variation of 30% (1 SD) was observed in the instantaneous source strength. Taking also the spread in implant size into account, the net variation in pulse duration amounted to 38%. CONCLUSION: An office hours PB boost regimen was designed for substitution of the CLDR boost in breast-conserving therapy on the basis of the BED. First treatment experience shows the office hour regimen to be convenient to the patients and no technical perturbations were encountered.

Brachytherapy with transperineal (125)Iodine seeds for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer. PATIENTS AND METHODS: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy. RESULTS: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone. CONCLUSIONS: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.

A new method for microdensitometer slit length correction of radiographic noise power spectra.

When the power spectrum of radiographic noise is estimated from scans obtained with a microdensitometer equipped with a rectangular slit, a bias is present due to the finite length of this slit. A method to correct for this bias was developed and was tested on both a simulated and a measured spectrum. No bias remains with our method, in situations where a conventional method shows a significantly biased result. Good agreement was found with the synthesized slit method, described by Sandrik and Wagner.

Filter materials for dose reduction in screen-film radiography.

A computer program was developed to calculate both integral absorbed dose in a water phantom and entrance exposure, for the imaging of iodine contrast with x-ray intensifying screens. The effect of filtration of the x-ray beam on integral absorbed dose and entrance exposure was studied for 27 different filter materials and four types of intensifying screens. The dose and exposure were calculated, keeping the image contrast and energy absorption in the screens constant. To check the validity of the calculations, a number of measurements were performed, the results of which agreed well with our calculations. A remarkable result is that dose and exposure reduction can be achieved almost equally well with conventional filters (aluminum and copper) as with a number of K-edge filters. This was found for situations commonly encountered in diagnostic radiology (60-80 kV, 20 cm water). This finding is in contrast to a number of earlier studies, in which K-edge filters were found to be superior to conventional filters.

Response of x-ray intensifying screens to scattered and primary radiation.

The energy dependence of the luminance ratio due to scattered and primary radiation has been determined for four types of X-ray intensifying screens. A water phantom of 30 cm X 30 cm X 20 cm was used as the scattering medium. Ten narrow band X-ray spectra were used as incident radiation: the mean energies of these spectra ranged from 28 to 84 keV. Using the monoenergetic data, results were calculated for broad spectra and compared with measured results for broad spectra. For tube voltages up to 50 kV the calculated results agreed well with the measured results: for higher tube voltages a small difference occurred.

Comparison of conformal radiation therapy techniques within the dynamic radiotherapy project 'Dynarad'.

The objective of the dynamic radiotherapy project 'Dynarad' within the European Community has been to compare and grade treatment techniques that are currently applied or being developed at the participating institutions. Cervical cancer was selected as the tumour site on the grounds that the involved organs at risk, mainly the rectum and the bladder, are very close to the tumour and partly located inside the internal target volume. In this work, a solid phantom simulating the pelvic anatomy was used by institutions in Belgium, France, Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated using both biological and physical criteria. The main purpose of this parallel evaluation is to test the value of biological and physical evaluations in comparing treatment techniques. It is demonstrated that the biological objective functions allow a much higher conformality and a more clinically relevant scoring of the outcome. Often external beam treatment techniques have to be combined with intracavitary therapy to give clinically acceptable results. However, recent developments can reduce or even eliminate this need by delivering more conformal dose distributions using intensity modulated external dose delivery. In these cases the reliability of the patient set-up procedure becomes critical for the effectiveness of the treatment.

Treatment of localized prostatic carcinoma using the transrectal ultrasound guided transperineal implantation technique.

Treatment of localized prostate cancer by ultrasonically guided transperineal 125I implantation, in contrast to open 125I implantation, may allow for ideal distribution of the seeds and may therefore lead to better treatment results. 46 patients with localized prostatic carcinoma (T1-T2, G1-G3, N0, M0) have been treated since 1985, using this new technique. The longest follow-up is 64 months (median 30 months). The irradiation implantation dose to the prostate was 160 Gy. Assessed by ultrasonography an average prostate volume reduction of 20% was achieved at 6 months, increasing to 24% at 12 months, 39% at 24 months and 56% at 48 months. To evaluate response of the primary tumor systematic ultrasonically guided needle biopsies from the previous malignant prostate areas were performed in all patients every 6 months during follow-up. Tumor-negative biopsies were obtained in 33% of patients at 12 months, 40% at 24 months, progressively increasing to 50% at 48 months. Three patients developed distant metastases, and 6 died, of whom 1 patient due to prostate cancer. Morbidity from implantation has been low and the erectile function was preserved in all patients at 12 months postimplantation. The high percentage of tumor-positive biopsies during follow-up indicates that this technique fails to cure a significant proportion of patients.