Interferometer experiment with independent local oscillators.

We have operated an interferometer with independent local oscillators and without any communication link of wide bandwidth between the elements of the interferometer. This makes operation possible at very long base lines because, heretofore, construction of the communications link has been the factor limiting the separation of the elements. In our system, coherence at the two elements is maintained through the use of two highly stable, atomic oscillators. The intermediate-frequency output signals are recorded at each element on a high-speed digital tape recorder. Interference fringes are produced later by cross-correlating the two tape records in a digital computer.

A comparison of medical physics training and education programs--Canada and Australia.

An overview and comparison of medical physics clinical training, academic education, and national certification/accreditation of individual professionals in Canada and Australia is presented. Topics discussed include program organization, funding, fees, administration, time requirements, content, program accreditation, and levels of certification/accreditation of individual Medical Physicists. Differences in the training, education, and certification/accreditation approaches between the two countries are highlighted. The possibility of mutual recognition of certified/accredited Medical Physicists is examined.

Development and characterization of a tissue equivalent plastic scintillator based dosimetry system.

High precision techniques in radiation therapy, such as intensity modulated radiation therapy, offer the potential for improved target coverage and increased normal tissue sparing compared with conformal radiotherapy. The complex fluence maps used in many of these techniques, however, often lead to more challenging quality assurance with dose verification being labor-intensive and time consuming. A prototype dose verification system has been developed using a tissue equivalent plastic scintillator that provides easy-to-acquire, rapid, digital dose measurements in a plane perpendicular to the beam. The system consists of a water-filled Lucite phantom with a scintillator screen built into the top surface. The phantom contains a silver coated plastic mirror to reflect scintillation light towards a viewing window where it is captured using a charge coupled device camera and a personal computer. Optical photon spread is removed using a microlouvre optical collimator and by deconvolving a glare kernel from the raw images. A characterization of the system was performed that included measurements of linear output response, dose rate dependence, spatial linearity, effective pixel size, signal uniformity and both short- and long-term reproducibility. The average pixel intensity for static, regular shaped fields between 3 cm X 3 cm and 12 cm x 12 cm imaged with the system was found to be linear in the dose delivered with linear regression analysis yielding a correlation coefficient r2 > 0.99. Effective pixel size was determined to be 0.53 mm/pixel. The system was found to have a signal uniformity of 5.6% and a long-term reproducibility/stability of 1.7% over a 6 month period. The system's ability to verify a dynamic treatment field was evaluated using 60 degrees dynamic wedged fields and comparing the results to two-dimensional film dosimetry. Results indicate agreement with two-dimensional film dosimetry distributions within 8% inside the field edges. With further development, this system promises to provide a fast, directly digital, and tissue equivalent alternative to current dose verification systems.

Modeling late effects in hypofractionated stereotactic radiotherapy.

PURPOSE: To investigate the effect of increasing fraction size on cell survival in late responding normal tissues. The hypothesis is that total dose can be reduced for constant tumor cell kill and there will be consequent advantage for some surrounding normal tissue cells. Also, the volume of normal tissue that can potentially be damaged by increasing fraction size is minimized by a high degree of dose conformation achievable in stereotactic radiotherapy (SRT). METHODS AND MATERIALS: The linear quadratic (LQ) model has been used to calculate the allowed reduction in total dose with increased fraction size, using tumor alpha/beta ratios of 5 Gy and 10 Gy. Effect on normal tissue is calculated using an alpha/beta ratio of 3 Gy. Maximum dose is normalized to 100% and the effect on normal tissue at different isodose levels assessed. A new quantity, the standard percentage dose, is proposed in order to describe a dose distribution in terms of an isodose distribution for a standard fraction size. Integral biologically effective dose (IBED) in the brainstem is calculated, where the variation with isocenter position and fraction size is considered. RESULTS: The decreasing total dose resulting from increasing the dose per fraction is found to reduce late normal tissue effect for low isodose levels. The threshold isodose level at which there is an advantage corresponds to the ratio of normal tissue to tumor alpha/beta ratios. Brainstem IBED for a higher dose per fraction increases relative to that for a low dose per fraction, when a larger volume of brainstem is covered by high isodose levels. CONCLUSION: Hypofractionation may be biologically sound when a small volume of normal tissue is covered by high isodose levels. There is a calculated advantage in using larger fractions in terms of cell survival at low isodose levels.

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: The aim of this work is to investigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors. METHODS AND MATERIALS: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m2 was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the confounding effect of the cisplatin. RESULTS: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at approximately 125 Gy3 corresponding to a brachytherapy dose of approximately 8 Gy per fraction. This value is approximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The data from the group of patients treated without cisplatin is comparable to the data from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison. CONCLUSION: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external beam irradiation in the head and neck region.

Rectal complications in patients with carcinoma of the cervix treated with concomitant cisplatin and external beam irradiation with high dose rate brachytherapy: a dosimetric analysis.

PURPOSE: This paper reports a dosimetric study of 43 patients treated with a combination of concomitant radiotherapy and chemotherapy (cisplatin) for locally advanced carcinoma of the cervix with the aim of investigating the correlation between the radiation dose to the rectum and the incidence of late rectal complications. METHODS AND MATERIALS: Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given weekly, concurrent with the last 3 weeks of external beam therapy, to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was given weekly throughout the duration of the external beam irradiation. The brachytherapy irradiated volume was reconstructed from the orthogonal treatment radiographs to accurately locate the reference points defined by the International Commission of Radiation Units and Measurements (ICRU), report 38. The doses calculated at these points were compared to in vivo dose measurements performed immediately prior to treatment. RESULTS: The group of patients who were calculated to have received a dose to the rectal reference point greater than the prescribed point A dose (9/13) had a significantly greater probability of development of late rectal complications compared to the group of patients who were calculated to have received less than the prescribed point A dose at this rectal point (7/30), p = 0.003. There was no correlation of rate of complication with the in vivo measured dose in the rectum, stage of disease, or age. At 40 months post treatment, the group of patients receiving the higher dose to the rectal reference point had an actuarial rate of serious (Grade 3 and 4) rectal complications of 46% compared to a rate of 14% in the remainder. In terms of survival, the group of patients receiving the higher dose to the rectal reference point have all survived, whereas the group of patients receiving the lower dose to the rectal reference point have a significantly different rate of survival of 72%, p = 0.046. CONCLUSION: This investigation has revealed a significant correlation between the dose calculated at the rectal point defined by the ICRU and the incidence of late rectal complications in patients with carcinoma of the cervix undergoing concomitant radiotherapy and chemotherapy. Thus, this rectal reference point appears to be a useful prognostic indicator of late rectal complications in these patients and we recommend that the brachytherapy dose delivered to this rectal point be limited to the dose prescribed to point A for treatment regimens using three fractions of 8-10 Gy each, limiting the total dose to this point, including the external beam component, to 76 Gy. Further study will be required to determine whether this rule should be applied to patients receiving irradiation alone.

Treatment results of high dose rate brachytherapy in patients with carcinoma of the cervix.

PURPOSE: The combination of external beam irradiation and low-dose-rate brachytherapy is known to be an effective form of treatment in carcinoma of the cervix and any change from this well-established therapeutic combination must be able to equal or improve the treatment results. Since 1984 we have been using high dose rate brachytherapy in conjunction with external beam irradiation for patients with carcinoma of the cervix. This paper reports our long term treatment results in terms of local disease control, survival, and complications. METHODS AND MATERIALS: Between January 1984 and December 1989, 187 previously untreated patients with carcinoma of the cervix underwent combined external beam irradiation and high dose rate brachytherapy. The International Federation of Gynecology and Obstetrics stage distribution of patients was as follows: I B = 15, II A = 35, II B = 68, III A = 9, III B = 54, IV A = 6. External beam irradiation to the whole pelvis was delivered by megavoltage irradiation with once-a-day fractionation, to a median dose of 4600 cGy. High dose rate brachytherapy was delivered by a high-dose-rate remote controlled afterloading unit, containing 20 spherical Cobalt 60 sources with a nominal activity of 19 GBq (0.5 Ci) at the time of installation, giving a typical dose rate to point A of 160 cGy/min, decreasing to about 80 cGy/min at the end of the 5-year study. One to 3 high dose rate brachytherapy treatments delivering 800 to 1000 cGy to point A were given weekly concurrently with the last 2 to 3 weeks of radiation therapy, or following its completion. Maximum rectal and bladder doses were routinely measured for each treatment. RESULTS: Overall 5-year actuarial survivals were as follows: I B = 72%, II A = 65%, II B = 66%, III A = 66%, III B = 45%. Five-year actuarial pelvic control rates were as follows: I B = 66%, II A = 83%, II B = 78%, III A = 88%, III B = 40%. At a median follow-up time of 54 months for patients at risk, 23 patients developed 25 complications attributable to radiotherapy (13 rectal, 3 bladder, 8 small bowel, 1 fistula) at a median time of 18 months following completion of treatment. Thirteen complications (7.6%) were grades 3 or 4. Patients with Stage II disease had a higher incidence of complications than patients with Stages I and III disease (p < 0.05). Rectal complications were significantly higher in patients who received a total rectal dose > 5400 cGy (p = 0.045). CONCLUSION: High-dose-rate brachytherapy treatment results are comparable to those obtained with low dose rate brachytherapy techniques. The use of three high dose rate brachytherapy insertions is a practical, economical, and safe treatment for patients with carcinoma of the cervix.

Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix.

PURPOSE: Prospective, single arm, Phase I/II trial performed to assess the efficacy and toxicity of the concomitant use of weekly cisplatin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. METHODS AND MATERIALS: Between December 1988 and April 1991, 50 previously untreated patients with bulky, locally advanced, squamous cell carcinoma entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pre-treatment staging procedures. The International Federation of Gynecology and Obstetrics stage distribution was as follows: IIA three patients, IIB seventeen, IIIA two, IIIB 25, and IVA three. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given on a weekly basis to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was also given weekly starting on day 1 of radiotherapy. RESULTS: With a median follow-up time of 27 months, complete response was seen in 88% (44/50) of the patients. The actuarial survival rate at 44 months was 65%. Total pelvic failure rate was 26% (13/50). Of the 44 patients who achieved a complete remission, only seven have failed in the pelvis. Distant disease was observed in 24% of the cases. Treatments were well tolerated with no patient requiring an interruption in the radiotherapy. However, the incidence of late gastrointestinal toxicity was high, with 10 patients developing a rectal ulcer (four colostomies for severe bleeding), two patients a small bowel obstruction, and two patients a recto-vaginal fistula. Moreover, gastrointestinal complications appeared sooner than expected, at a median follow-up time of 11 months after completion of treatment. CONCLUSION: The combination of weekly cisplatin and radiotherapy appears to be a very effective regimen for patients with locally advanced carcinoma of the cervix, but resulted in a relatively high frequency of late gastrointestinal complications.

The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy.

OBJECTIVE: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. MATERIALS & METHODS: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. RESULTS: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. CONCLUSION: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue.

Bromperidol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in psychoses.

Bromperidol is a close structural analogue of haloperidol. Both agents possess similar pharmacodynamic properties which are consistent with central antidopaminergic activity. The available clinical data from non-comparative and comparative trials have shown that bromperidol possesses antipsychotic activity. Its overall efficacy was slightly greater than chlorpromazine and perphenazine, and similar to or slightly better than haloperidol in a small number of comparative studies. Bromperidol frequently displayed a faster onset of action than these comparative agents and there have been reports of bromperidol causing an activating effect. However, extrapyramidal side effects occurred with similar frequency and severity after bromperidol compared with the 3 reference drugs. Data from additional controlled clinical trials are required to confirm the comparative antipsychotic efficacy of bromperidol and to assess whether it possesses any advantages in certain sub-types of schizophrenia.

Loprazolam. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in insomnia.

Loprazolam is a 1,4-benzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia. As loprazolam has a half-life of 7 to 8 hours in healthy adults it may have advantages over longer-acting hypnotics, particularly when residual sedative effects on the day after ingestion are undesirable, although at doses greater than 1 mg residual sedation may occur. In addition, it may reduce daytime anxiety, following a hypnotic dose the night before, more effectively than the short-acting drug, triazolam. In short term comparative studies loprazolam was clearly superior to placebo, and was at least as effective as triazolam, flurazepam, nitrazepam, flunitrazepam or temazepam in hastening sleep onset, reducing nocturnal awakenings and increasing total sleep duration and quality. In the small number of patients with chronic insomnia who have received extended treatment with loprazolam, no evidence of tolerance has occurred, although rebound insomnia was evident 3 days after drug withdrawal in several studies. Thus, with its 'intermediate' elimination half-life, loprazolam would appear to have some potential advantages over both long- and short-acting hypnotics in selected patients, although further studies are needed to fully elucidate its place in therapy.

Female preponderance in diuretic-associated hypokalemia: a retrospective study in seven long-term care facilities.

A retrospective review of the medical records of 161 geriatric nursing-home patients receiving diuretics alone or in combination with potassium supplements or potassium sparing-diuretics revealed a 13.7 per cent overall prevalence of hypokalemia. The prevalence of hypokalemia in patients receiving diuretics alone, diuretics with potassium supplements, and potassium-sparing diuretics with kaliuretic diuretics were similar. However, there was a significantly higher prevalence of hypokalemia in women (16.4 per cent) compared with men (3.0 per cent), P less than 0.05. In patients taking non-chloride salts of potassium, there was a significantly higher prevalence of hypokalemia than in those taking the chloride salt (3.6 per cent vs. 8 per cent, P less than 0.025). Seven per cent of patients taking diuretics with potassium supplements and 11.5 per cent of patients taking potassium-sparing diuretics had hyperkalemia. Thus, although many elderly women taking diuretics may have hypokalemia routine potassium supplementation for all non-digitalized geriatric patients receiving diuretics does not seem to be indicated.

A practical technique for verification of three-dimensional conformal dose distributions in stereotactic radiosurgery.

The trend toward conformal techniques in stereotactic radiosurgery necessitates an accurate and practical method for verification of irregular three-dimensional dose distributions. This work presents the design and evaluation of a phantom system facilitating the measurement of conformal dose distributions using one or more arrays of up to 20 radiographic films separated by 3.2 mm-thick tissue-equivalent spacers. Using Electron Gamma Shower version 4 (EGS4) Monte Carlo simulation, we show that for 6 MV radiosurgical photon beams this arrangement preserves tissue-equivalence to within 1%. The phantom provides 0.25 mm in-plane spatial resolution and multiple sets of films may be used to resample the dose volume in orthogonal planes. Dedicated software has been developed to automate the process of ordering and orienting of scanned film images, conversion of scanned pixel value to dose, resampling of one or more sets of film images and subsequent export of images in DICOM format for coregistration of planned and measured dose volumes. Calculated and measured isodose surfaces for a simple, circular-beam treatment agree to within 1.5 mm throughout the dose volume. For conformal radiosurgical applications, the measured and planned dose distributions agree to within the uncertainty of the manufacture of irregularly shaped collimators. The sensitivity of this technique to minor spatial inaccuracies in beam shaping is also demonstrated.

The use of radiographic film for linear accelerator stereotactic radiosurgical dosimetry.

The measurement of stereotactic radiosurgical dose distributions requires an integrating, high-resolution dosimeter capable of providing a spatial map of absorbed dose. Although radiographic film is an accessible dosimeter fulfilling these criteria, for larger radiotherapy photon fields the sensitivity of film emulsion exhibits significant dependencies on both depth in phantom and field size. We have examined the variation of film sensitivity over the ranges of depths and field sizes of interest in radiosurgery with a 6 MV photon beam. While for large (20cm x 20cm) fields the potential error in dose due to the variation of the film response with depth reaches 15%, the corresponding maximum error for a 2.5 cm diameter radiosurgical beam is 1.5%. This uncertainty was observed to be comparable in magnitude to that produced by variation in processing conditions (1.1%) and by varying the orientation of the film plane relative to the beam central axis (1.5%). The dependence of emulsion sensitivity on field size has been observed to be negligible for fields ranging in diameter from 1.0 cm to 4.0 cm. The source of the dependence of film sensitivity has been illustrated by using an EGS4 Monte Carlo simulation for large fields to illustrate significant increases in the photon spectrum below 400 keV with depth in phantom. In contrast, relative increase of this low-energy component is negligible for radiosurgical photon fields.

Experimental determination of dosimetry functions of Ir-192 sources.

Experimental data related to the dosimetric characteristics of Ir-192 brachytherapy sources are limited. The aim of this work was to obtain the dosimetry functions required by the American Association of Physicists in Medicine Task Group 43 for both a low and a high dose-rate iridium-192 brachytherapy source through dose measurements in a water-equivalent phantom. Dose measurements have been performed using lithium fluoride thermoluminescent detectors positioned in a polystyrene phantom at distances from the source that vary from 1 to 10 cm, with 1 cm intervals, and at angles that vary from 0 degree to 170 degrees with 10 degrees intervals. The anisotropy functions, radial dose functions, and dose rate constants were determined for both brachytherapy sources. The precision of results obtained on those relatively fine intervals of angles and distances provides clinics with the possibility to use and interpolate the complete data sets for treatment planning.

Verification of the correspondence between CT-stimulated and treatment beams.

A single phantom technique has been developed to verify the full CT simulation and treatment-beam delivery procedures. The phantom consists of a target delineated by thin copper strips, affixed to therapy verification film, and inserted securely between two slices of water-equivalent material. The target is defined with the aid of the copper strips, and the position of the isocenter and beam parameters such as field size, and gantry and collimator angle are determined by CT simulation. With these parameters, the phantom is subsequently irradiated by the linear accelerator in the treatment position. Correspondence between the planned and the irradiated region is determined by the position of the copper strips on the film. The technique is a simple and practical method for verifying the entire CT simulation and treatment-beam delivery processes, and provides a permanent record of the correspondence between the planning digitally reconstructed radiographs (DRR) and the actual beam delivered.

Analysis of treatment parameters for conformal shaped field stereotactic irradiation: comparison with non-coplanar arcs.

The change in configuration from circular convergent arcs to shaped static fields for stereotactic radiosurgery raises questions regarding comparability of dose distributions between the techniques. This study aims to quantify the optimization of planning parameters to achieve dose distributions minimizing dose to healthy tissue. Dose volume histograms were calculated and averaged from several patient treatments to measure dose homogeneity and healthy tissue irradiation inherent in variable PTV margins, the effect of increasing numbers of static shaped fields, the dose fall-off outside the PTV and of field placement. Our results show that adding a 2 mm margin around the target volume when defining field shapes maximizes dose coverage and homogeneity without substantially increasing the volume of healthy tissue irradiated to high dose levels. We demonstrate that 5-6 static fields may be optimal for typical lesions and that placement of these fields may not always play a major role in healthy tissue sparing. This work illustrates a systematic approach to conformal static field treatment plan optimization which relies on the prior determination of parameters such as optimum margin width to account for field penumbra. Complex irregularly shaped lesions still require careful patient-specific assessment of healthy tissue irradiation.

A halo-ring technique for fractionated stereotactic radiotherapy.

Stereotactic radiosurgery has become established as an effective treatment modality for certain non-malignant brain diseases such as arteriovenous malformations. This paper describes an extension of our linear accelerator-based radiosurgical technique to fractionated treatment of intracranial disease. The fractionated stereotactic radiotherapy technique expands the use of the modality by sparing normal cells within the treatment volume thus improving the therapeutic ratio. The first treatment is given using a stereotactic frame both for target localization and patient immobilization. The frame is then removed and subsequent treatments use a standard neurosurgical halo-ring for patient immobilization. The halo-ring is left in place on the skull for the duration of the course of treatment. Thus the physical requirements for fractionation pertain firstly to the patient immobilization and target localization using the halo-ring and secondly to the stringent quality assurance procedures required to maintain spatial accuracy under these new conditions. We describe a sensitive and effective technique for checking the rotational beam parameters and collimator alignment which we use immediately prior to treatment to ensure adequate accuracy of dose delivery to the target volume.

Receiver operating characteristics of RadioVisioGraphy.

The diagnostic utility of intra-oral images obtained from the RVG second generation digital imaging system are compared with standard film images with the use of receiver operating characteristic analysis. Ten phantoms were constructed, each with 8 extracted teeth that had 12 approximal surfaces per phantom with holes drilled randomly to simulate approximal caries. Three images of each phantom were tested: a conventional film image, a thermal paper print, and a screen image. The images were rated by 26 dentists at separate sessions according to their confidence in the visibility of the simulated caries. A series of receiver operating characteristics curves were computed from the resulting 3120 decisions that indicate consistently greater success at detection of the holes on the film images. A full statistical analysis is given, and recommendations are made with respect to the use of this unit.