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Biomedical subjects

B G Clark

Publications and source records attributed to B G Clark.

At least 19 recordsLinked to original sources

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.

Biomimetic Materials↗

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.

Algorithms↗

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.

Biophysical Phenomena↗

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.

Brain Neoplasms↗

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.

Dose-Response Relationship, Radiation↗

Stereotactic radiation in primary brain tumors in children and adolescents.

To evaluate treatment outcome and morbidity of stereotactic external-beam irradiation (SEBI) in pediatric patients, we reviewed 14 children treated with SEBI, using a 10-MV isocentric linear accelerator at McGill University between 1988 and 1994. The median follow-up was 46 months (range 6-82 months). The median age was 14 years. There were 8 low-grade astrocytomas, 3 neuromas and 4 other histologies. Twelve patients received fractionated treatments. The median collimator diameter was 2.5 cm (range 1-5 cm). The median biological effective dose delivered to the entire tumor volume was 57 Gy for astrocytomas and 43 Gy for the other histologies. The overall actuarial survival rate and disease-free survival rate at 5 years were 83 and 62%, respectively. For the patients with low-grade astrocytomas, the 5-year survival and disease-free survival rates were 100 and 60%, respectively. Four children had recurrence at a median of 37 months. Four patients developed treatment-related complications: 1 had edema alone, 2 had necrosis and 1 had edema associated with necrosis. Neither the physical nor radiobiological parameters were predictive of the treatment outcome or the treatment complications. Stereotactic irradiation is a valid option for progressive nonresectable tumors in children.

Adolescent↗

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.

Adolescent↗

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.

Computer Simulation↗

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.

Anisotropy↗

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.

Antineoplastic Agents↗

Isolated vaginal recurrences in endometrial carcinoma: treatment results using high-dose-rate intracavitary brachytherapy and external beam radiotherapy.

PURPOSE: To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma following total abdominal hysterectomy and bisalpingo-oophorectomy (TAH BSO). MATERIALS AND METHODS: Twenty patients originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or II) following TAH BSO developed isolated vaginal recurrences and were referred to our radiation oncology department for definitive treatment. The median time between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Median prescribed dose was 3500 cGy to the vagina mucosa surface for the HDRB only group. These patients were followed for a median duration of 47.5 months following treatment for isolated vaginal recurrence. RESULTS: Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications. Three patients developed grade 2 late complications from treatment; all 3 were from the combined modality group (HDRB + EBRT). CONCLUSION: The use of HDRB resulted in high complete response rates and durable long-term disease-specific survival in a substantial percentage of patients. To our knowledge, this study represents the first published results on treatment of vaginal recurrences with HDRB. Although the number of patients in this study is small, treatment results compare favorably to those obtained from patients treated with low-dose-rate brachytherapy +/- EBRT from other studies.

Adenocarcinoma↗

High-dose-rate brachytherapy as the primary treatment of medically inoperable stage I-II endometrial carcinoma.

Between 1984 and 1992, 27 patients with clinical stage I-II histologically proven adenocarcinoma of the endometrium who had significant medical risks precluding surgery underwent radiotherapy (RT) as the primary treatment. The median age at diagnosis was 74 years. There were 20 patients (74%) with stage I and 7 patients (26%) with stage II disease. Patients were treated with high-dose-rate brachytherapy (HDRB) alone (19/27) or with a combination of external-beam RT and HDRB (2 stage I; 6 stage II). HDRB was delivered using a cobalt-60 HDR remote afterloading unit, with a median dose of 2000 cGy to point A, in two to three fractions given once a week. All HDRB treatments were performed under spinal anesthesia on an outpatient basis. External-beam irradiation to the pelvis was given using 4- to 6-MV photons and a median dose of 4200 cGy was delivered. In all patients, vaginal bleeding was controlled within a few days after completion of RT. With a median follow-up of 47 months, the 8-year disease-specific survival rate was 76%. Patients with stage I had an 8-year survival rate superior to that of patients with stage II (95% vs 21%, P < 0.001). No complications were experienced during HDRB. Late serious complications were seen in 3 patients (11%). Based on this retrospective review, primary RT with HDRB appears to be an effective and safe treatment for those patients with medically inoperable clinical stage I endometrial carcinoma. Because HDRB is given on an outpatient basis, it is an attractive option for these patients. However, in stage II disease the results of treatment are poor and RT alone should be considered only when the surgical risks are too high.

Aged↗

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.

Confidence Intervals↗

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.

Brachytherapy↗

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.

Adult↗

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.

Adult↗

The use of integral activity to assess scheduled radioactive source changes for brachytherapy.

The development of afterloading brachytherapy devices using radioactive sources with relatively short half-lives has meant that several source changes are required per year. We present here a simple method to evaluate the ability of the supplier to deliver the scheduled amount of activity. Using the integrated activity of the source during the period of its clinical use, a comparison between the scheduled and delivered activity can be quantified.

Brachytherapy↗