A simple technique for craniospinal radiotherapy in the supine position.
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Adult↗
Biomedical subjects
Glenn Bauman
Publications and source records attributed to Glenn Bauman.
A comparison of prostate IMRT and helical tomotherapy class solutions.
The purpose of this study was to assess a variety of potential IMRT class solutions as compared to a helical tomotherapy (HT) class solution for localized prostate cancer. Target and critical structures were contoured on 10 prostate cancer patient CT datasets. HT treatment plans were compared to four different IMRT approaches by paired t-tests. HT prostate planning generally provided treatment plans with excellent target homogeneity and favorable critical structure sparing when compared to conventional IMRT.
Humans↗
Comparative planning evaluation of intensity-modulated radiotherapy techniques for complex lung cancer cases.
BACKGROUND AND PURPOSE: Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance. PATIENTS AND METHODS: Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate PTV2 and 1cm margin around elective nodes for PTV1 resulting in PTV1 volumes larger than 1000 cm(3) in 13 of the 15 patients. 3D conformal and IMRT plans were generated on a commercial treatment planning system (TheraPlan Plus, Nucletron) with various combinations of beam energies and gantry angles. A 'dose quality factor' (DQF) was introduced to correlate the plan quality with patient specific parameters. RESULTS: A good correlation was found between the quality of the plans and the overlap between PTV1 and lungs. The patient feature factor (PFF), which is a product of several pertinent characteristics, was introduced to facilitate the choice of a particular technique for a particular patient. CONCLUSIONS: This approach may allow the evaluation of different treatment options prior to actual planning, subject to validation in larger prospective data sets.
Carcinoma, Non-Small-Cell Lung↗
Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: a radiobiologic analysis.
PURPOSE: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. METHODS AND MATERIALS: Five prostate cancer patients with approximately 16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. RESULTS: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). CONCLUSIONS: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.
Dose Fractionation, Radiation↗
Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: in regard to Kupelian et al. (Int J Radiat Oncol Biol Phys 2005;630:1024-1028).
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Carcinoma, Non-Small-Cell Lung↗
Fractionated radiotherapy techniques.
A convergence of advances in patient immobilization and localization, patient imaging, beam shaping and delivery, and treatment planning has led to considerable improvement in the ability to deliver highly conformal radiation treatments by radiosurgical or fractionated radiotherapy techniques. The selection of the "best" treatment technique for any given patient needs to consider the morphology of the target and regional organs at risk as well as available technology and institutional expertise.
Brain Neoplasms↗
Bub1 up-regulation and hyperphosphorylation promote malignant transformation in SV40 tag-induced transgenic mouse models.
Rodents do not naturally develop prostate cancer. Currently, most widely used genetically engineered mouse prostate cancer models use SV40 T/tag oncogene. To understand the mechanism underlying prostate cancer development in transgenic and knock-in SV40 Tag mouse models, we did cDNA microarray analyses, comparing gene expression profiles of prostate cancer tissues from early-, late-, and advance-stage androgen-independent prostate cancers. Of the 67 genes that were up-regulated by > or = 10-fold, 40 are known to be required for chromosome stability. In particular, the spindle checkpoint component Bub1 was persistently up-regulated from early to advanced androgen-independent prostate cancer lesions. Significantly, Bub1, which is required for accurate chromosome segregation during mitosis, has recently been reported to bind SV40 Tag. Consistent with a spindle checkpoint defect, flow cytometry experiments indicate that advanced androgen-independent prostate cancer tumors exhibit aneuploidy, along with up-regulation of levels of both Bub1 mRNA and Bub1 protein or hyperphosphorylation. Importantly, up-regulation and hyperphosphorylation of Bub1 were also observed in established human prostate cancer cell lines and in clinical studies. Furthermore, analysis of human prostate cancer lines showed impaired spindle checkpoint function and endoreduplication following exposure to spindle toxins. Small interfering RNA-mediated repression of Bub1 in the human prostate cancer line PC-3 restrained cell proliferation, an effect mimicked by inhibition of mitogen-activated protein kinase, an upstream activator of Bub1. Thus, by perturbing Bub1 function, our observations suggest a new mechanism whereby the SV40 Tag oncoprotein promotes chromosomal instability and aneuploidy in transgenic mouse prostate cancer models. Whereas the exact details of this mechanism remain unclear, our novel findings raise the possibility of exploiting Bub1 as a new therapeutic target in the treatment of prostate cancer, the most common cancer in adult men in North America.
Animals↗
Impact of geometric uncertainties on evaluation of treatment techniques for prostate cancer.
PURPOSE: To assess the impact of patient repositioning and internal organ motion on prostate treatment plans using three-dimensional conformal and intensity-modulated radiotherapy. METHODS AND MATERIALS: Four-field, six-field, and simplified intensity-modulated arc therapy plans were generated for 5 prostate cancer patients. The planning target volume was created by adding a 1-cm margin to the clinical target volume. A convolution model was used to estimate the effect of random geometric uncertainties during treatment. Dose statistics, tumor control probabilities, and normal tissue complication probabilities were compared with and without the presence of uncertainty. The impact of systematic uncertainties was also investigated. RESULTS: Compared with the planned treatments, the delivered dose distribution with random geometric uncertainties displayed an increase in the apparent minimal dose to the prostate and seminal vesicles and a decrease in the rectal volume receiving a high dose. This increased the tumor control probabilities and decreased the normal tissue complication probabilities. Changes were seen in the percentage of prostate volume receiving 100% and 95% of the prescribed dose, and the minimal dose and tumor control probabilities for the target volume. In addition, the volume receiving at least 65 Gy, the minimal dose, and normal tissue complication probabilities changed considerably for the rectum. The simplified intensity-modulated arc therapy technique was the most sensitive to systematic errors, especially in the anterior-posterior and superior-inferior directions. CONCLUSION: Geometric uncertainties should be considered when evaluating treatment plans. Contrary to the widely held belief, increased conformation of the dose distribution is not always associated with increased sensitivity to random geometric uncertainties if a sufficient planning target volume margin is used. Systematic errors may have a variable effect, depending on the treatment technique used.
Algorithms↗
Tomotherapy planning of small brain tumours.
Helical tomotherapy (HT) combines a rotating intensity modulated fan beam with integrated CT imaging for high precision radiotherapy. HT plans for 12 patients with small brain tumours were compared with five other radiotherapy techniques. Proton techniques gave overall the best results, while HT was shown to produce better target dose uniformity (average SD=1.3%) and kept irradiation of organs at risk as good as other photon methods.
Adenoma↗
Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review.
BACKGROUND AND PURPOSE: The purpose was to develop a systematic review that would address the following question: what is the role of radiopharmaceuticals in the palliation of metastatic bone pain in adults with uncomplicated, multifocal painful bone metastases whose pain is not controlled with conventional analgesic regimens? The outcomes of interest are pain response, analgesic consumption, overall survival, adverse effects and quality of life. MATERIALS AND METHODS: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes. RESULTS: Six randomized phase III trials, two randomized phase II trials and one randomized crossover trial of strontium-89 were reviewed. A randomized phase III trial comparing strontium-89 plus cisplatin with strontium-89 plus placebo reported a significantly higher proportion of patients experiencing pain relief for a significantly longer duration with strontium-89 plus cisplatin. A randomized phase III trial comparing adjuvant strontium-89 with placebo following radiotherapy reported a higher proportion of pain-free patients with strontium-89. Patients who received strontium-89 also experienced fewer new sites of bone pain. A second, but underpowered study failed to confirm these results. In one randomized trial of strontium-89 versus radiotherapy (hemibody or local), patients treated with strontium-89 developed fewer new sites of pain. In a second trial comparing strontium-89 versus local radiotherapy, median overall survival was improved with radiotherapy, while pain response and time-to-progression were similar in the two groups. One randomized phase III trial reported no difference in pain relief between strontium-89 and placebo. Three randomized phase III trials and two randomized phase II trials investigating samarium-153 were reviewed. In a randomized phase III trial of three different doses of samarium-153, the pain responses were similar for all three doses. In a randomized phase III trial of two different doses of samarium-153 versus placebo, the complete pain response rate was significantly higher with the higher dose of samarium-153 compared with placebo. In a randomized phase III trial comparing samarium-153 with placebo, significant differences favouring samarium-153 were reported for pain and opiate use. In addition, one randomized phase III trial, two randomized phase II trials, one randomized crossover trial and 13 phase II or phase I trials of rhenium, one phase I trial of tin-117 m and one phase II trial of phosphorus-32 were reviewed. The majority of patients treated in trials of radiopharmaceuticals where histology was specified had metastatic breast cancer (approximately 5-10% of patients reported), metastatic hormone-refractory prostate cancer (80-90% of patients reported) or metastatic lung cancer (5-10% of patients reported). Information on histologic subtype was not available for a significant proportion of patients treated on trials (30-40% of patients reported). CONCLUSIONS: Use of single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be considered as a possible option for the palliation of multiple sites of bone pain from metastatic cancer where pain control with conventional analgesic regimens is unsatisfactory and where activity on a bone scan of the painful lesions is demonstrated. Ongoing clinical research should seek to establish the benefit of newer radiopharmaceuticals and radiopharmaceuticals in combination with other systemic therapies.
Bone Neoplasms↗
Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.
The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the margin size seemed the only sure way to reduce the NTCP significantly, irrespective of the IGART technique employed. In escalating the dose with the iso-NTCP constraint, the largest average gain in dose was observed with the "tattoo registration" technique, followed by the "CTV registration" and "bone registration" techniques. This is attributed to the fact that in three of the five patients, the "tattoo registration" technique yielded the lowest NTCP, hence a greater window of opportunity to escalate the dose was possible with this technique. However, the variation among the five patients was also largest with the "tattoo registration" technique where, in the case of one patient, the required dose actually needed to be below the original prescription dose of 70 Gy to satisfy the iso-NTCP constraint. This was not the case with the "CTV registration" technique where positive and similar dose escalation was allowed on all five patients. Based on these data, an attractive dose escalation strategy may be to implement the "CTV registration" technique (for consistent dosimetric coverage) for daily target localization in combination with a margin reduction (for increased normal tissue sparing).
Dose Fractionation, Radiation↗
A pilot study of regional participation in a videoconferenced multidisciplinary genitourinary tumor board.
A successful pilot study of a videoconferenced multidisciplinary genitourinary tumor board involving 21 physicians over six geographic sites for a 6-month period is reported. The majority of cases presented at the tumor board were of prostate or bladder origin. Specific recommendations around management, patient referral or clinical trial eligibility were made in the majority of cases presented. Physician satisfaction with the rounds was high and participation beyond the pilot has continued. Scheduling in order to provide maximum access/participation has been the main logistical challenge with the rounds.
Humans↗
Planning evaluation of radiotherapy for complex lung cancer cases using helical tomotherapy.
Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/-4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.
Carcinoma, Non-Small-Cell Lung↗
In regard to Fiorino et al.: Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer (Int J Radiat Oncol Biol Phys 2003;57:953-962).
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Gastrointestinal Hemorrhage↗
Radiotherapy for pediatric central nervous system tumors: a regional cancer centre experience.
INTRODUCTION: The purpose of this review was to analyze outcomes for pediatric patients treated for more common (non-low grade glioma) primary central nervous system (CNS) tumors at a Regional (tertiary) Cancer Center. Comparison to reported results from other regional centres and results from the contemporary literature were made. MATERIAL AND METHODS: The records of pediatric patients treated with radiotherapy at the London Regional Cancer Center (LRCC) for more common (non-low grade glioma) primary CNS tumors between 1980 and 2001 were reviewed. Details regarding tumor presentation, treatment and outcome were analyzed. RESULTS: Eighty-eight patients were eligible for the review. Twenty-nine patients with malignant glioma, 37 patients with medulloblastoma or primitive neuroectodermal tumor (PNET), 15 patients with brainstem glioma, 4 with ependymoma and 3 with germ cell tumors were treated during this time period. Average follow-up for the group was 5 years (range 4 months to 19 years). Five-year overall, progression free and cause specific survival were 45, 42 and 50%, respectively. For patients with malignant glioma median progression free and overall survival was 20 and 29 months. For patients with brainstem glioma median progression free and overall survival was 9 and 13 months. For medulloblastoma, 5-year progression free, and overall survival was 60 and 59%. CONCLUSIONS: RESULTS of this retrospective review of pediatric patients treated at a regional cancer center for primary CNS tumors (other than low grade glioma) were comparable to contemporary results reported by other Canadian centers and North American co-operative group trials.
Adolescent↗
Asymmetric fan beams (AFB) for improvement of the craniocaudal dose distribution in helical tomotherapy delivery.
Helical tomotherapy (HT) is a novel radiotherapy technique that utilizes intensity modulated fan beams that deliver highly conformal dose distributions in a helical beam trajectory. The most significant limitation in dose delivery with a constant fan beam thickness (FBT) is the penumbra width of the dose distribution in the craniocaudal direction, which is equivalent to the FBT. We propose to employ a half-blocked fan beam at start and stop location to reduce the penumbra width by half. By opening the jaw slowly during the helical delivery until the desired FBT is achieved it is possible to create a sharper edge in the superior and inferior direction from the target. The technique was studied using a tomotherapy beam model implemented on a commercial treatment planning system (Theraplan Plus V3.0). It was demonstrated that the dose distribution delivered using a 25 mm fan beam can be improved significantly, to reduce the dose to normal structures located superiorly and inferiorly of the target. Dosimetry for this technique is straightforward down to a FBT of 15 mm and implementation should be simple as no changes in couch movement are required compared to a standard HT delivery. We conclude that the use of asymmetric collimated fan beams for the start and stop of the helical tomotherapeutic dose delivery has the potential of significantly improving the dose distribution in helical tomotherapy.
Algorithms↗
Low-grade glioma: current management and controversies.
The question of optimal management of patients with low-grade gliomas continues to generate considerable controversy. Retrospective studies have helped delineate prognostic factors for patients with these tumors as well as the relative efficacy of surgery, radiation and chemotherapy. Results of recently completed and ongoing prospective, multi-institutional trials will help guide the treatment of these patients in the future. Other advances include the molecular characterization of these tumors that should assist in selection of existing and development of future therapies.
Brain Neoplasms↗
The use of conformal radiotherapy and the selection of radiation dose in T1 or T2 low or intermediate risk prostate cancer - a systematic review.
BACKGROUND AND PURPOSE: The purpose was to develop a systematic review that would address the following questions: (a) when single-modality treatment external-beam radiotherapy is selected as the modality of choice, what is the role of three-dimensional (3D) conformal radiotherapy in treating clinically localized (T1, T2/NO, NX/MO) prostate cancer? The outcomes of interest are biochemical freedom from failure (bNED) rates, clinical recurrence-free survival, disease-specific survival and acute and late toxicity; (b) what is the appropriate dose and fractionation prescription in this clinical setting? MATERIALS AND METHODS: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes. RESULTS: One randomized controlled trial comparing conventional radiotherapy to conformal therapy with dose escalation reported bNED rates. Three additional randomized controlled trials reported acute or chronic late outcome assessments. Additionally, phase II studies of dose escalation in sequential patient cohorts and non-randomized comparative assessments of dose-response and bNED rates in controlled analyses were reviewed. There is convincing evidence from randomized trials that the use of conformal therapy reduces acute and late treatment-related morbidity. There is preliminary evidence suggesting that when external-beam therapy alone is used to treat patients, conformal therapy with dose-escalation is more efficacious than doses of 70Gy. The increased efficacy appears to be predominantly seen in the subset of patients with intermediate-risk disease (PSA 10-20). There is conflicting evidence of the efficacy of dose-escalation in patients with low initial PSA (<10) and in patients with initial PSA greater than 20. Conformal radiotherapy at a dose of 78Gy appears to be relatively safe with no increase in acute or late effects compared with conventional treatment (up to 70Gy) so long as appropriate technological principles are considered. CONCLUSIONS: Patients who have external-beam radiotherapy should be treated using a 3D conformal technique. Patients with intermediate-risk disease (PSA 10-20) who are treated with external-beam radiotherapy alone should be offered doses of 75-78Gy in 180-200cGy fractions.
Disease-Free Survival↗